Boston University Medical Campus
Human Genetics

DNA Tests (Descriptions and CPT codes)

46,XY DISORDERS OF SEX DEVELOPMENT (NR5A1-RELATED) and OVARIAN INSUFFICIENCY

GENE: NR5A1/SF1 (nuclear receptor subfamily 5, group A, member 1)
CHROMOSOMAL LOCATION: 9q33
MODE OF INHERITANCE: heterozygous/homozygous mutations described, sporadic

Mutations within the NR5A1/SF1 have been described in 13% of patients with 46,XY disorders of sex development with or without adrenal insufficiency. Recently, mutations within the NR5A1/SF1 gene have been described in patients with 46,XX complete gonadal dysgenesis and in patients with 46,XX primary ovarian insufficiency.

Our laboratory offers DNA sequencing of all coding exons as well as MLPA analysis of select exons within the NR5A1/SF1 gene. Prenatal diagnosis is available when a mutation has been identified in the family.

CPT codes:
46,XY DSD/OVARIAN INSUFFICIENCY (NR5A1) (SEQUENCING)
83890(1);83891(12);83894(1);83898(6);83892(6);83904(12);83909(12);83912(1)

46,XY DSD/OVARIAN INSUFFICIENCY (NR5A1) (MLPA)
83890(1);83898(1);83896(40);83909(1);83914(1);83912(1)

46,XY DSD/OVARIAN INSUFFICIENCY (NR5A1) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

AARSKOG-SCOTT SYNDROME (Faciogenital Dysplasia)

GENE: FGD1 (FYVE, RhoGEF and PH domain containing 1)
CHROMOSOMAL LOCATION: Xp11.21
MODE OF INHERITANCE: X-linked

Aarskog-Scott syndrome is an X-linked condition characterized by short stature, hypertelorism, syndactyly, and a characteristic “shawl” scrotum. Cognitive impairment and/or behavioral disorders occur in approximately 30-40% of affected individuals. Our laboratory offers DNA sequencing of all coding exons (exons 1-18) as well as MLPA analysis for the detection of whole-exon or whole-gene deletions within FGD1.

This assay may be ordered alone or as part of the X-linked Mental Retardation (XLMR) panel. Prenatal testing is available when a mutation is known in the family.

CPT codes:
AARSKOG-SCOTT (FGD1) (SEQUENCING)
83890(1);83891(30);83892(15);83894(1);83898(15);83904(30);83909(30);83912(1)

AARSKOG-SCOTT (FGD1) (MLPA)
83890(1);83896(30);83898(1);83909(1);83914(30)83912(1)

AARSKOG-SCOTT (FGD1) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

ACUTE MYELOID (or MYELOGENOUS) LEUKEMIA

GENES: FLT3 (fms-related tyrosine kinase 3)
NPM1 (nucleophosmin family, member 1)
CHROMOSOMAL LOCATION: 13q12 (FLT3); 5q35 (NPM1)
REGIONS ANALYZED: ITD AND D835 within FLT3, and NPM1 exon 12 sequencing
INCIDENCE: An internal tandem duplication (ITD) of the juxtamembrane domain-coding sequence of the FLT3 gene (FLT3-ITD) is found in 20-25% of adult acute myeloid leukemia (AML) and at a lower frequency in childhood AML. D835 mutations within the activation loop of the second tyrosin kinase domain (TKD) of FLT3 (FLT3-TKD) occur in 5%-14% of patients. Approximately 45-60% of patients with chromosomally normal AML carry NPM1 gene mutations.

Acute myeloid leukemia (AML) is the most common childhood malignancy, however AML is generally an adult onset condition with the average age of diagnosis of 67 years. Chromosome analysis at the time of diagnosis provides the most important prognostic information in adults with AML, but 40-50% of patients do not have clonal chromosomal aberrations. Somatic mutations in chromosomally normal AML have been identified and include internal tandem duplications (ITDs), and mutations of the tyrosine kinase domain (TKD) of the FLT3 gene. In addition, somatic mutations have been described in the NPM1. FLT3-ITD in patients with chromosomally normal AML is associated with leukocytosis and poor prognosis. Approximately 45-60% of patients with chromosomally normal AML carry NPM1 gene mutations and are associated with a favorable clinical outcome when FLT3-ITD are absent.

CPT codes:
ACUTE MYELOID (or MYELOGENOUS) LEUKEMIA (AML) MUTATION PANEL

FLT3 D835 MUTATION
83890(1);83891(1);83892(1);83909(1);83898(1);83912(1)

FLT3 ITD (INTERNAL TANDEM DUPLICATION) MUTATION 83890(1);83891(1);83892(1);83894(1);83898(1);83912(1)

NPM1 EXON12 SEQUENCING 83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

ALPHA-THALASSEMIA MENTAL RETARDATION SYNDROME (Chudley-Lowry Syndrome, XLMR-Hypotonic Facies Syndrome, Smith-Fineman-Myers MR Syndrome)

GENE: ATRX (transcriptional regulator ATRX)
CHROMOSOMAL LOCATION: Xq13
MODE OF INHERITANCE: X-linked

Alpha-thalassemia X-linked mental retardation (ATRX) syndrome is characterized by distinctive craniofacial features, genital anomalies, and severe developmental delays with hypotonia and mental retardation. Our laboratory offers DNA sequencing of all coding exons (exons 1-35) of the ATRX gene. This analysis detects up to 95% of mutations in individuals with a clinical diagnosis of ATRX syndrome.

This assay may be ordered alone or as part of the X-linked Mental Retardation (XLMR) panel. Prenatal testing is available when a mutation is known in the family.

CPT codes:
ALPHA-THALASSEMIA MENTAL RETARDATION SYNDROME (Chudley-Lowry Syndrome, XLMR-Hypotonic Facies Syndrome, Smith-Fineman-Myers MR Syndrome)
ATRX (SEQUENCING)
83890(1);83891(70);83892(35);83894(4);83898(35);83904(70);83909(70);83912(1)

ATRX (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

ANGELMAN SYNDROME

GENE: UBE3A (ubiquitin protein ligase E3A)
CHROMOSOMAL LOCATION: 15q11-q13
MODE OF INHERITANCE: deletion; uniparental disomy; imprinting defects; some autosomal dominant rearrangements

Angelman syndrome (AS) is characterized by severe developmental delay or mental retardation, severe speech impairment, gait ataxia, and a unique behavior that includes frequent laughing, smiling, and excitability. Microcephaly and seizures are also common. Angelman syndrome is caused by a deletion or disruption of the maternal chromosome 15q11-q13 gene region. Our methylation-sensitive assay detects deletions of the maternal chromosome 15, uniparental disomy of the paternal chromosome 15, and imprinting defects. Approximately 78% of Angelman syndrome cases are detectable using this assay. This direct DNA analysis for Angelman syndrome is recommended for the confirmation of a diagnosis in a patient with or without a family history of the condition. Karyotyping parents of an affected child and methylation studies of a fetus are available for prenatal diagnosis. Further studies, including FISH deletion analysis and uniparental disomy studies (which require parental blood samples), are available and recommended following a positive test result.

CPT codes:
ANGELMAN SYNDROME (METHYLATION)
83890(1);83891(1);83892(1);83894(1);83896(1);83897(1);83912(1)

ANGELMAN SYNDROME (UBE3A SEQUENCING)
83890(1);83891(30);83892(15);83894(1);83898(15);83904(30);83909(30);83912(1)

ANGELMAN SYNDROME (UBE3A MLPA)
83890(1);83892(1);83896(88);83898(2);83909(2);83914(2);83912(1)

ANGELMAN SYNDROME (UBE3A KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

ANGELMAN-LIKE SYNDROME (X-linked syndromic MR- Christianson type)

GENE: SLC9A6 (solute carrier family 9 member 6)
CHROMOSOMAL LOCATION: Xq26.3
MODE OF INHERITANCE: X-linked

Mutations in the SLC9A6 gene are thought to be responsible for an X-linked mental retardation syndrome with Angelman syndrome-like features including microcephaly, seizures, ataxia, and absent speech. The clinical spectrum of features seem to resemble Angelman syndrome in younger patients and Christianson syndrome in older patients.

Our laboratory offers DNA sequencing of all coding exons (1-16) of the SLC9A6 gene.

This assay may be ordered alone or as part of the X-linked Mental Retardation (XLMR) panel. Prenatal testing is available when a mutation is known in the family.

CPT codes:
SLC9A6 (SEQUENCING)
83890(1);83891(32);83894(1);83898(16);83892(16);83904(32);83909(32);83912(1)

SLC9A6 (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

ASHKENAZI JEWISH PANEL (Bloom Syndrome, Canavan Disease, Factor XI deficiency, Familial Dysautonomia, Fanconi Anemia, Gaucher Disease, Glycogen storage disease type 1A (von Gierke disease), Mucolipidosis type IV, Maple Syrup Urine disease type 1B (MSUD), Niemann-Pick Disease (type A), and Tay-Sachs Disease)

				# of Mutations	Detection Rate	Carrier Frequency
Bloom syndrome				1	99%	1:111
Canavan disease				3	97%	1:40
Factor XI deficiency				2	96%	1:8
Familial Dysautonomia				2	99%	1:32
Fanconi Anemia group C				1	99%	1:92
Gaucher disease				3	92%	1:13
Glycogen storage disease type 1A				2	93%	1:71
Mucolipidosis type IV				2	95%	1:81
Maple Syrup Urine disease type 1B (MSUD)				3	99%	1:122
Niemann-Pick disease (type A)				3	94%	1:90
Tay-Sachs disease				5	98%	1:30

ASHKENAZI JEWISH CARRIER SCREEN PANEL TEST INCLUDES: 11 gene panel
(TAY-SACHS/GAUCHER’S/CANAVANS/FAMILIAL DYSAUTONOMIA/NIEMANN-PICK DISEASE TYPE A/FANCONI ANEMIA/BLOOM SYNDROME/ GLYGOGEN STORAGE DISEASE 1A/MUCOLIPIDOSIS TYPE IV/MAPLE SYRUP URINE DISEASE TYPE 1B/FACTOR XI)

CPT codes for complete panel of 11 genes:
83890(1);83891(1);83900(6);83901(11);83894(1);83892(6);83896(28);83789(28);83912(1)

CPT codes by individual gene:
BLOOM SYNDROME
83890(1);83891(1); 83898(1);83894(1);83892(1);83896(1);83789(1);83912(1)

CANAVAN DISEASE (3 MUTATIONS)
83890(1);83891(1);83900(1);83901(1);83894(1);83892(2);83896(3);83789(3);83912(1)

FACTOR XI DEFICIENCY
83890(1);83891(1);83900(1);83894(1);83892(1);83896(2);83789(2);83912(1)

FAMILIAL DYSAUTONOMIA (2 MUTATIONS)
83890(1);83891(1);83898(2);83894(1);83892(2);83896(2);83789(2);83912(1)

FANCONI ANEMIA TYPE C
83890(1);83891(1); 83898(1);83894(1);83892(1);83896(1);83789(1);83912(1)

GAUCHER DISEASE
83890(1);83891(1);83900(1);83901(2);83894(1);83892(2);83896(4);83789(4);83912(1)

GLYCOGEN STORAGE DISEASE 1A (VON GIERKE DISEASE)
83890(1);83891(1);83900(1);83894(1);83892(1);83896(2);83789(2);83912(1)

MUCOLIPIDOSIS TYPE IV (MCOLN1)
83890(1);83891(1);83900(1);83894(2);83898(1);83892(1);83896(1);83789(1);83912(1)

MAPLE SYRUP URINE DISEASE TYPE 1B (BCKDHB)
83890(1);83891(1);83900(1);83901(1);83894(1);83892(2);83896(3);83789(3);83912(1)

NIEMANN-PICK DISEASE TYPE A (3 MUTATIONS)
83890(1);83891(1);83900(1);83901(1);83894(1);83892(1);83896(3);83789(3);83912(1)

TAY-SACHS DISEASE
83890(1);83891(1);83892(3);83894(4);83898(4);83912(1)

ATAXIA PANELCONDITIONS: SCA10, SCA12, SCA17, Dentatorubral-Pallidoluysian Atrophy (DRPLA)
GENES: ATXN10 (ataxin-10)
PPP2R2B (serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform)
TBP (TATA-box-binding protein)
ATN1 (atrophin-1)
CHROMOSOMAL LOCATIONS: 22q13 (ATXN10); 5q32 (PPP2R2B); 6q27 (TBP); 12p13.3 (ATN1)
MODE OF INHERITANCE: autosomal dominant for all

The hereditary ataxias are a group of genetic disorders characterized by slowly progressive incoordination of gait often associated with poor coordination of hands, speech, and eye movements.

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder characterized by cerebellar ataxia and seizures. The mutation associated with SCA10 is a pentanucleotide repeat (ATTCT) expansion located in intron 9 of the SCA10 gene. Anticipation has been observed in some families with paternal transmission of the pentanucleotide repeat expansion. Normal individuals are found to have a range of 10-29 repeats, while affected individuals exhibit allele sizes greater than 800 repeats. Our laboratory offers testing for the SCA10 pentanucleotide expansion mutation by PCR and Ladder assays.

Spinocerebellar ataxia type 12 (SCA12) is an autosomal dominant disorder characterized by action tremor of the upper extremities progressing to ataxia and other cerebellar and cortical signs. The mutation associated with SCA12 is a triplet repeat (CAG) expansion located in the promoter region of the SCA12 gene. Normal individuals are found to have a range of 4-32 repeats, while affected individuals exhibit allele sizes greater than 51 repeats. Our laboratory offers testing for the SCA12 triplet expansion mutation by PCR and Ladder assays.

Spinocerebellar ataxia type 17 (SCA17) is an autosomal dominant disorder characterized by ataxia, dementia, chorea, and dystonia. The mutation associated with SCA17 is a triplet repeat (CAA/CAG) expansion located in exon 3 of the SCA17 gene. Normal individuals are found to have a range of 25-42 repeats. A reduced penetrance range of 43-48 repeats is reported, while affected individuals exhibit allele sizes greater than or equal to 49 repeats. Our laboratory offers testing for the SCA17 triplet expansion mutation by PCR analysis.

Dentatorubral pallidoluysian atrophy (DRPLA) is an autosomal dominant disorder characterized by myoclonus, seizures, ataxia, choreoathetosis and dementia. The mutation associated with DRPLA is a triplet repeat (CAG) expansion located in exon 5 of the DRPLA gene. Normal individuals are found to have a range of 6-35 repeats, while affected individuals exhibit allele sizes greater than or equal to 48 repeats. Our laboratory offers testing for the DRPLA triplet expansion mutation by PCR analysis.

The ataxias listed above have the common characteristics of wide-based unsteady gait, lack of coordination, dysarthria, scanning and explosive speech, and hyperreflexia. Unless otherwise requested, all of the above disorders will be tested. If a particular disorder is suspected, gene analysis of that specific disorder can be done first. If negative, the full ataxia panel will follow. Prenatal diagnosis is available for families in which the presence of a trinucleotide repeat expansion has been demonstrated. Direct DNA analysis of the ataxia genes is recommended for symptomatic patients, with or without a family history of ataxia. DNA analysis of asymptomatic patients with a positive family history of an autosomal dominant ataxia is also possible. Predictive testing of these patients, including prenatal diagnosis, introduces complex issues and risks. For this reason we recommend genetic counseling throughout the testing process.

CPT codes:
ATAXIA PANEL
SPINOCEREBELLAR ATAXIA TYPE 10
83890(1);83891(1);83894(1);83898(1);83912(1)

SPINOCEREBELLAR ATAXIA TYPE 10 LADDER ASSAY (WHEN REQUIRED)
83894(1);83898(1);83912(1)

SPINOCEREBELLAR ATAXIA TYPE 12
83890(1);83891(1);83894(1);83898(1);83912(1)

SPINOCEREBELLAR ATAXIA TYPE 12 LADDER ASSAY (WHEN REQUIRED)
83894(1)L83898(1)L83912(1)

SPINOCEREBELLAR ATAXIA TYPE 17
83890(1);83891(1);83894(1);83898(1);83912(1)

DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY (DRPLA)
83890(1);83891(1);83894(1);83898(1);83912(1)

“SYSTEMATIC TESTING” FOR MOVEMENT DISORDERS LISTED ABOVE INCLUDES:
SCA-10,12,17, and DRPLA, ANALYZED SEQUENTIALLY
FIRST TEST
83890(1);83891(1);83894(1);83898(1);83912(1)
EACH ADDITIONAL TEST
83894(# tests);83898(# tests);83912(#tests)

BCR/ABL (Philadelphia Chromosome)

GENES: Abelson oncogene (ABL) and Breakpoint Cluster Region (BCR)
CHROMOSOMAL LOCATION: t(9;22)(q34;q11)
INCIDENCE: 90-95% of chronic myeloid leukemia (CML) patients
11-30% of adult acute lymphoblastic leukemia (ALL) patients MODE OF INHERITANCE: somatic cell genetic disorder

A direct RNA test is available to identify patients with a translocation of the ABL oncogene into the BCR gene on chromosome 22. The fused transcript of the two genes has been implicated in the malignant process of both chronic myeloid leukemia patients and acute lymphocytic leukemia patients. Direct RNA analysis for the BCR/ABL rearrangement is useful for prognostication of patients with CML or AML. Concomitant chromosome analysis is recommended.

CPT codes:
BCR/ABL (PHILADELPHIA CHROMOSOME)
83890(1);83891(1);83894(2);83898(4);83902(1);83912(1)

BLOOM SYNDROME

GENE: BLM (DNA helicase Rec Q protein-like 3)
CHROMOSOMAL LOCATION: 15q26.1
MUTATION ANALYZED: 2281del6bp/ins7bp
CARRIER FREQUENCY: 1 in 111 (Ashkenazi Jewish)
MODE OF INHERITANCE: autosomal recessive

Individuals with Bloom syndrome typically have short stature, pigmentation abnormalities, and an increased susceptibility to infections, respiratory illnesses, and certain malignancies, such as leukemia. Bloom syndrome causes chromosomal instability and sister chromatid exchange. The 2281del6bp/ins7bp is present in at least 98% of affected individuals. This assay may be ordered alone or as part of the Ashkenazi Jewish panel. Prenatal testing is available when a mutation is known in the family.

CPT codes:
BLOOM SYNDROME
83890(1);83891(1); 83898(1);83894(1);83892(1);83896(1);83789(1);83912(1)

BRANCHIO-OCULO-FACIAL SYNDROME

GENE: TFAP2A (transcription factor AP-2 alpha)
CHROMOSOMAL LOCATION: 6p24
MODE OF INHERITANCE: autosomal dominant

Branchio-Oculo-Facial syndrome (BOFS) is a disorder of the first and second pharyngeal
arches that includes thinned, erythematous cutaneous defects in the cervical or infra- and/or supra-auricular region, ocular anomalies, nasolacrimal duct obstruction, and characteristic craniofacial features.
Our laboratory offers DNA sequencing of all coding exons as well as the detection of a whole gene deletion via MLPA analysis of the TFAP2A gene. Prenatal testing is available when a mutation is known in the family.

CPT codes:
BOF SYNDROME (TFAP2A) (SEQUENCING)
83890(1);83891(16);83894(1);83898(8);83892(8);83904(16);83909(16);83912(1)

BOF SYNDROME (TFAP2A) (MLPA)
83890(1);83891(1);83900(1);83901(15);83909(1);83912(1)

BOF SYNDROME (TFAP2A) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

BREAST CANCER (3 Common Ashkenazi Jewish Mutations only)

GENE: BRCA1 GENE: BRCA2
CHROMOSOMAL LOCATION: 17q21 CHROMOSOMAL LOCATION: 13q12.3
MUTATIONS ANALYZED: 185delAG, 5382insC MUTATIONS ANALYZED: 6174delT
INCIDENCE OF THESE MUTATIONS: approximately 2.5% of Ashkenazi Jews
MODE OF INHERITANCE: autosomal dominant

These three mutations are the most common among the Ashkenazi Jewish population. It is not known at this time what percentage of familial breast cancer cases are caused by these mutations. However, for cases in which the family is Ashkenazi Jewish and there is clear evidence of early onset breast cancer in multiple first or second degree relatives, our laboratory can offer screening for these common BRCA1 and BRCA2 mutations. Prior to testing, we strongly urge all patients to have genetic counseling to review their risk of breast and/or ovarian cancer, to discuss possible findings from screening, and to discuss the relevance of these findings to the management of their health care. Documentation of cancer reported in the family history is advised. Routine testing of all Jewish women for these mutations is not recommended.

CPT codes:
BREAST CANCER BRCA-1 AND BRCA-2 MUTATIONS (3 JEWISH MUTATIONS)
83890(1);83891(1);83892(2);83894(3);83898(3);83912(1)

CANAVAN DISEASE

GENE: ASPA (Aspartoacylase)
CHROMOSOMAL LOCATION: 17pter-p13
MUTATIONS ANALYZED: E285A, Y231X, and A305E
CARRIER FREQUENCY: 1 in 40 (Ashkenazi Jewish)
MODE OF INHERITANCE: autosomal recessive

Canavan Disease is a severe progressive genetic disorder of the CNS that occurs most frequently in children of Ashkenazi (European) Jewish ancestry. Symptoms appear after the first few months and may include macrocephaly, hypotonia, and poor head control. The disease typically progresses with lack of muscle development, seizures, optic atrophy, and feeding problems. The large majority of children with Canavan Disease die before age five. The American College of Obstetrics & Gynecology (ACOG) recommends carrier screening for couples in which at least one person is of Ashkenazi Jewish ancestry. Direct DNA analysis is also available for patients who have signs or symptoms suggestive of this disorder. The assay used detects 98% of mutations in the Ashkenazi Jewish population and approximately 40% of mutations in individuals with non-Ashkenazi Jewish ancestry. This assay may be ordered alone or as part of the Ashkenazi Jewish panel. Prenatal testing is available when a mutation is known in the family.

CPT codes:
CANAVAN DISEASE (3 MUTATIONS)
83890(1);83891(1);83900(1);83901(1);83894(1);83892(2);83896(3);83789(3);83912(1)

CARDIOFACIOCUTANEOUS SYNDROME

GENES: BRAF (B-Raf proto-oncogene serine/threonine-protein kinase)
MAP2K1 (MEK1; mitogen-activated protein kinase kinase 1)
MAP2K2 (MEK2; mitogen-activated protein kinase kinase 2)
KRAS (GTPase KRas)
CHROMOSOMAL LOCATIONS: 7q34 (BRAF); 12p12.1 (KRAS); MAP2K1 (15q21) ; MAP2K2 (7q32)
MODE OF INHERITANCE: autosomal dominant, typically de novo

Cardiofaciocutaneous (CFC) syndrome is characterized by short stature, congenital heart defects, ectodermal abnormalities, and developmental delay/mental retardation. The clinical features of CFC syndrome often overlap with those of Noonan and Costello syndromes. Sequence analysis of the BRAF gene detects missense mutations in approximately 75%-80% of individuals with a clinical diagnosis of CFC syndrome. MAP2K1 and MAP2K2 mutations have been reported in 15%-20% of individuals with CFC syndrome. Mutations in KRAS have been found in <5% of individuals with CFC syndrome. Hence, this above comprehensive analysis performed by our laboratory is expected to detect approximately 95% of individuals with CFC syndrome.

Testing in CFC syndrome is offered as comprehensive, simultaneous CFC testing of all 4 CFC genes (most time effective, with a significantly shorter turn-around-time) or specific testing of any of these genes can be ordered. Once a mutation in the proband is identified, mutation-specific testing in relatives and prenatal diagnosis is available.

CPT codes:
CARDIOFACIOCUTANEOUS SYNDROME (CFC) PANEL (BRAF;MAP2K1;MAP2K2; KRAS)

CPT codes for complete panel of 4 genes:
83890(1);83891(90);83892(45);83894(3);83898(45); 83904(90);83909(90);83912(1)

CPT codes by individual gene:
BRAF (SEQUENCING)
83890(1);83891(36);83892(18);83894(2);83898(18);83904(36);83909(36);83912(1)

BRAF (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

MAP2K1 (SEQUENCING)
83890(1);83891(22);83892(11);83894(1);83898(11);83904(22);83909(22);83912(1)

MAP2K1 (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

MAP2K2 (SEQUENCING)
83890(1);83891(22);83892(11);83894(1);83898(11);83904(22);83909(22);83912(1)

MAP2K2 (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

KRAS (SEQUENCING)
83890(1);83891(10);83892(5);83894(1);83898(5);83904(10);83909(10);83912(1)

KRAS (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

CHARCOT-MARIE-TOOTH DISEASE, TYPES 1B, 2I, 2J

GENE: Myelin protein zero (MPZ)
CHROMOSOMAL LOCATION: 1q22
MODE OF INHERITANCE: autosomal dominant

Charcot-Marie-Tooth disease is a sensorineural peripheral polyneuropathy. Affecting approximately 1 in 2,500 individuals, CMT is the most common inherited disorder of the peripheral nervous system. Autosomal dominant, autosomal recessive, and X-linked forms have been recognized. CMT1 accounts for 50% of all CMT cases. Approximately 5-10% of CMT1 is type 1B. Our laboratory offers DNA sequencing of all six coding exons in the MPZ gene, which detects >99% of individuals with CMT1B. Prenatal diagnosis is available when a mutation has been identified in a family.

CPT codes:
CHARCOT-MARIE-TOOTH DISEASE (TYPES 1B, 2I, 2J) (MPZ) (SEQUENCING)
83890(1);83891(1);83894(10);83898(5);83904(10);83912(1)

CHARCOT-MARIE-TOOTH DISEASE (TYPES 1B, 2I, 2J) (MPZ) (KNOWN MUTATION)
83890(1);83891(1);83894(2);83898(1);83904(2);83912(1)

CHARGE SYNDROME

GENE: CHD7 (chromodomain helicase DNA-binding protein 7)
CHROMOSOMAL LOCATION: 8q12.1
MODE OF INHERITANCE: autosomal dominant, typically de novo

CHARGE syndrome is characterized by iris colobomas, congenital heart defects, choanal atresia/stenosis, growth retardation, abnormal genitalia, and ear anomalies/sensorineural deafness. Our laboratory offers DNA sequencing of all coding exons (exons 2-38) as well as MLPA analysis for the detection of whole-exon or whole-gene deletions or duplications within CHD7. These analyses detect approximately 65% of mutations in individuals with clinically diagnosed CHARGE syndrome. Prenatal diagnosis is available when a mutation has been identified in a family.

CPT codes:
CHARGE SYNDROME (CHD7) (SEQUENCING)
83890(1);83891(76);83892(38);83894(2);83898(38);83904(76);83909(76);83912(1)

CHARGE SYNDROME (CHD7) (MLPA)
83890(1);83896(37);83898(1);83909(1);83914(37);83912(1)

CHARGE SYNDROME (CHD7) (KNOWN MUTATION)
83890(1);83891(1);83894(2);83898(1);83904(2);83912(1)

COFFIN LOWRY SYNDROME

GENE: RSK2/RPS6KA3 (ribosomal protein S6 kinase alpha-3)
CHROMOSOMAL LOCATION: Xp22.2-p22.1
MODE OF INHERITANCE: X-linked

Coffin-Lowry syndrome (CLS) is characterized by short stature, typical facial features (downslanting palpebral fissures and bulbous nasal tip), short, fleshy, tapering fingers, and severe to profound mental retardation. Clinical findings in females are variable. Our laboratory offers DNA sequencing of all coding exons (exons 1-22) as well as MLPA analysis of select exons for the detection of whole-exon or whole-gene deletions or duplications within RSK2/RPS6KA3.
This assay may be ordered alone or as part of the X-linked Mental Retardation (XLMR) panel. Prenatal testing is available when a mutation is known in the family.

CPT codes:
COFFIN LOWRY SYNDROME (RSK2, RPS6KA3) (SEQUENCING)
83890(1);83891(44);83894(3);83898(22);83892(22);83904(44);83909(44);83912(1)

COFFIN LOWRY SYNDROME (RSK2, RPS6KA3) (MLPA)
83890(1);83891(1);83900(1);83901(43);83909(1);83912(1)

COFFIN LOWRY SYNDROME (RSK2, RPS6KA3) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

CONGENITAL BILATERAL ABSENCE OF THE VAS DEFERENS (CBAVD)

GENE: CFTR (cystic fibrosis transmembrane conductance regulator)
CHROMOSOMAL LOCATION: 7q31
MODE OF INHERITANCE: autosomal recessive

Congenital bilateral absence of the vas deferens (CBAVD), which causes male infertility, may occur in isolation or as a manifestation of cystic fibrosis. At least one form of the disorder is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene, which is located on chromosome 7. Most cases of CBAVD without renal agenesis are related to CF, with approximately 75% having at least 1 detectable cystic fibrosis mutation and 65% having an elevated sweat chloride. Our laboratory offers the CF100 mutation panel for individuals with CBAVD and their partners.

CPT codes:
CONGENITAL BILATERAL ABSENCE OF THE VAS DEFERENS (CBAVD) (100 MUTATIONS)
83890(1);83891(1);83900(18);83901(15);83894(1);83896(86);83892(18);83789(18);83912(1)

CONGENITAL BILATERAL ABSENCE OF THE VAS DEFERENS (CBAVD) (5T MUTATION OR ANY SINGLE MUTATION)
83890(1);83891(1);83894(1);83896(1);83898(1);83892(1);83789(1);83912(1)

CONGENITAL BILATERAL ABSENCE OF THE VAS DEFERENS (CBAVD) (CFTR SEQUENCING)
83890(1);83891(58);83894(2);83898(29);83892(29);83904(58);83909(58);83912(1)

CONGENITAL BILATERAL ABSENCE OF THE VAS DEFERENS (CBAVD) (MLPA)
83890(1);83898(2);83896(43);83909(2);83914(2);83912(1)

CONGENITAL BILATERAL ABSENCE OF THE VAS DEFERENS (CBAVD) (KNOWN SEQUENCE MUTATION)
83890(1);83891(2);83894(1);83898(1);83892(1);83904(2);83909(2);83912(1)

CONGENITAL CONTRACTURAL ARACHNODACTYLY (Beals syndrome)

GENE: FBN2 (fibrillin 2)
CHROMOSOMAL LOCATION: 5q23-q31
MODE OF INHERITANCE: autosomal dominant

Congenital contractural arachnodactyly (CCA) is a connective tissue disorder characterized by a Marfan-like appearance, “crumpled” ear appearance, and multiple contractures of the major joints. Scoliosis is also often observed. Although patients with CCA may have marfanoid habitus, they do not exhibit ectopia lentis. Our laboratory offers sequencing of all coding exons (exons 1-65) of the FBN2 gene which detects 27-75% of mutations in patients with a clinical diagnosis of Congenital Contractural Arachnodactyly.
Prenatal diagnosis is available when a mutation has been identified in a family.

CPT codes:
CONGENITAL CONTRACTURAL ARACHNODACTYLY (Beals syndrome) (FBN2) (SEQUENCING)
83890(1);83891(130);83892(65);83894(4);83898(65); 83904(130);83909(130);83912(1)

CONGENITAL CONTRACTURAL ARACHNODACTYLY (Beals syndrome (FBN2) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

CONNEXIN 30 (NON-SYNDROMIC DEAFNESS) DELETION ASSAY

GENE: GJB6 (CONNEXIN 30)
CHROMOSOMAL LOCATION: 13q12
MODE OF INHERITANCE: autosomal recessive

Inherited deafness accounts for at least 50% of all hearing loss and is mostly autosomal-recessive and non-syndromic. The connexin 30 deletion spans over 340 kb, representing the most common mutation reported in the connexin-30 gene. This deletion is detected in 10-15% of patients with non-syndromic hearing loss who have one mutation in the connexin-26 gene.

CPT codes:
CONNEXIN-30 (NON-SYNDROMIC DEAFNESS) DELETION ASSAY
83890(1);83891(1);83900(1);83894(1);83901(1);83912(1)

COSTELLO SYNDROME

GENE: HRAS (GTPase HRas)
BRAF (B-Raf proto-oncogene serine/threonine-protein kinase)
KRAS (GTPase KRas)
CHROMOSOMAL LOCATION: 11p15.5 (HRAS); 7q34 (BRAF); 12p12.1 (KRAS)
MODE OF INHERITANCE: autosomal dominant, typically de novo

Costello syndrome is characterized by coarse facial features, failure to thrive in infancy, short stature, curly/sparse fine hair, facial and/or perianal papillomata, loose soft skin with deep palmar and plantar creases, and developmental delay /mental retardation. Sequence analysis of all coding exons (exons 1-4) of the HRAS gene detects mutations in approximately 80%-90% of individuals with a clinical diagnosis of Costello syndrome. Mutations in KRAS and BRAF have also been reported in individuals with Costello syndrome.

Testing in Costello syndrome is offered as comprehensive, simultaneous Costello testing of all 3 Costello genes (most time effective, with a significantly shorter turn-around-time) or specific testing of any of these genes can be ordered. Once a mutation in the proband is identified, mutation-specific testing in relatives and prenatal diagnosis is available.

CPT codes:
COSTELLO SYNDROME (HRAS;KRAS;BRAF)

CPT codes for complete panel of 3 genes:
83890(1);83891(56);83892(28);83894(2);83898(28);83904(56);83909(56);83912(1)

CPT codes by individual gene:
HRAS (SEQUENCING)
83890(1);83891(10);83894(1);83898(5);83892(5);83904(10);83909(10);83912(1)

HRAS (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

KRAS (SEQUENCING)
83890(1);83891(10);83892(5);83894(1);83898(5);83904(10);83909(10);83912(1)

KRAS (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

BRAF (SEQUENCING)
83890(1);83891(36);83892(18);83894(2);83898(18);83904(36);83909(36);83912(1)

BRAF (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

CYSTIC FIBROSIS

GENE: CFTR (cystic fibrosis transmembrane conductance regulator)
CHROMOSOMAL LOCATION: 7q31
CARRIER FREQUENCY: 1 in 25
MODE OF INHERITANCE: autosomal recessive

Cystic fibrosis affects epithelia of the respiratory tract, exocrine pancreas, intestine, male genital tract, hepatobiliary system, and exocrine sweat glands, resulting in complex multisystem disease. Pulmonary disease is the major cause of morbidity and mortality in CF. The majority of cases of cystic fibrosis have a demonstrable mutation in the CFTR gene. Specifically, our panel of 40 mutations detects 98% of mutations in the Ashkenazi Jewish population and up to 90% of mutations in the Northern European population. Detection rates for individuals of other ethnicities vary. Direct DNA analysis of the cystic fibrosis gene is recommended for the confirmation of a diagnosis in a patient with or without a family history of CF. Prenatal diagnosis is available for a family with a confirmed case of cystic fibrosis, or when there is a suspicion that the fetus is affected (i.e. echogenic bowel). In addition, the American College of Obstetrics & Gynecology (ACOG) recommends CF carrier screening to all couples in which at least one person is Caucasian. Cystic fibrosis carrier screening should also be available to couples of other ethnic backgrounds. If one member of a couple is found to be a CF carrier, then our CF100 mutation panel is recommended for their partner.

CPT codes:
CYSTIC FIBROSIS (40 MUTATIONS)
83890(1);83891(1);83900(6);83901(7);83894(1);83896(31);83892(6);83789(6);83912(1)

CYSTIC FIBROSIS (100 MUTATIONS)
83890(1);83891(1);83900(18);83901(15);83894(1);83896(86);83892(18);83789(18);83912(1)

CYSTIC FIBROSIS (5T MUTATION OR ANY SINGLE MUTATION)
83890(1);83891(1);83894(1);83896(1);83898(1);83892(1);83789(1);83912(1)

CYSTIC FIBROSIS (CFTR SEQUENCING)
83890(1);83891(58);83894(2);83898(29);83892(29);83904(58);83909(58);83912(1)

CYSTIC FIBROSIS (CFTR MLPA)
83890(1);83898(2);83896(43);83909(2);83914(2);83912(1)

CYSTIC FIBROSIS (CFTR KNOWN SEQUENCE MUTATION)
83890(1);83891(2);83894(1);83898(1);83892(1);83904(2);83909(2);83912(1)

DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY (DRPLA)

GENE: ATN1 (atrophin-1)
CHROMOSOMAL LOCATION: 12p
INCIDENCE: < 1 in 100,000
MODE OF INTERITANCE: autosomal dominant with anticipation

DRPLA is a progressive disorder characterized by ataxia, myoclonus, epilepsy, and progressive intellectual deterioration in children, and ataxia, choreoathetosis, and dementia or character changes in adults. The mean age of onset of 30 years (age range 1-62 years). In both familial and sporadic cases of DRPLA there is a demonstrable trinucleotide repeat expansion (CAG) believed to be the causative factor of the condition. Direct DNA analysis of the ATN1 gene is recommended for patients who show symptoms of the condition, with or without a family history of cerebellar ataxia and dementia. DNA analysis of patients with a positive family history who do not have signs or symptoms of DRPLA is also possible. Predictive testing of these patients, including prenatal diagnosis, introduces complex issues and risks. For this reason we recommend pre-test genetic counseling for DRPLA.

CPT codes:
DENTATORUBRAL-PALLIDOLUYSIAN ATROPHY (DRPLA)
83890(1);83891(1);83894(1);83898(1);83912(1)

DNA / LYMPHOBLAST BANKING

We are able to isolate DNA or establish a cell line from either a blood or tissue sample to be banked in our laboratory for possible future genetic testing. This service requires a consent form and requisition form complete with the name and address of the individual and/or legal guardian. While the Center for Human Genetics does not intend to cease operation of the DNA/lymphoblast banking facility, should any change affecting the storage of samples occur, the Center for Human Genetics will use reasonable efforts to notify each donating family to determine the disposition of the sample.

CPT codes:
DNA BANKING
83890(1);83891(1);83912(1)

EHLERS-DANLOS SYNDROME TYPE IV (VASCULAR TYPE)

GENE: COL3A1 (collagen proα 1(III))
CHROMOSOMAL LOCATION: 2q31
MODE OF INHERITANCE: autosomal dominant

Ehlers-Danlos syndrome, vascular type (EDS IV) is a connective tissue disorder that represents the most severe form of the Ehlers-Danlos syndromes. The syndrome is typically characterized by thin, translucent skin, easy bruising, characteristic facial appearance, and arterial, intestinal, and/or uterine fragility. Vascular rupture or dissection and gastrointestinal perforation or organ rupture are the presenting signs in 70% of adults. Our laboratory offers DNA sequencing of all coding exons (exons 1-51) as well as MLPA analysis of select exons for the detection of whole-exon or whole-gene deletions or duplications within COL3A1. These analyses detect >98% of mutations in individuals with clinically diagnosed EDS type IV. Prenatal diagnosis is available when a mutation has been identified in a family.

CPT codes:
EHLERS-DANLOS TYPE IV SYNDROME (COL3A1) (SEQUENCING)
83890(1);83891(102);83892(51);83894(3);83898(51);83904(102);83909(102);83912(1)

EHLERS-DANLOS TYPE IV SYNDROME) (COL3A1) (MLPA)
83890(1);83896(44);83898(1); 83909(1);83912(1);83914(1)

EHLERS-DANLOS TYPE IV SYNDROME (COL3A1) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

EPILEPSY AND MENTAL RETARDATION (FEMALE-RESTRICTED)

GENE: PCDH19 (protocadherin 19)
CHROMOSOMAL LOCATION: Xq13.3
MODE OF INHERITANCE: X-linked (sex-limited)

This disorder is characterized by epilepsy and mental retardation with the phenotype being restricted only to females.

Our laboratory offers DNA sequencing of all coding exons (1-5) of the PCDH19 gene.
This assay may be ordered alone or as part of the X-linked Mental Retardation (XLMR) panel. Prenatal testing is available when a mutation is known in the family.

CPT codes:
EPILEPSY WITH MENTAL RETARDATION (PCDH19) (SEQUENCING)
83890(1);83891(14);83894(1);83898(7);83892(7);83904(14);83909(14);83912(1)

EPILEPSY WITH MENTAL RETARDATION (PCDH19) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

FACTOR V LEIDEN

GENE: F5 (coagulation factor V)
CHROMOSOMAL LOCATION: 1q21-25
INCIDENCE: 2-8% of the Caucasian population
MODE OF INHERITANCE: autosomal dominant

The most common hereditary blood clotting disorder is due to a specific mutation in the gene for factor V called the Leiden mutation (Arg506Gln). Persons who are heterozygous for the Leiden mutation have a 7-fold increased risk for thrombosis, and those who are homozygous have an 80-fold increased risk for thrombosis. Persons who are at risk to carry the factor V mutation are those with a family history of early onset stroke, deep vein thrombosis, thromboembolism, pregnancy associated with thrombosis/embolism, hyperhomocystinemia, and multiple miscarriage. Individuals with the mutation are at increased risk of thrombosis in the setting of oral contraceptive use, trauma, and surgery. Direct DNA analysis of the Factor V and prothrombin (see below) mutations are now recommended for at-risk patients because of the importance of therapy and antithrombotic prophylaxis.

CPT codes:
FACTOR V LEIDEN MUTATION
83890(1);83891(1);83892(1);83894(1);83898(1);83912(1)

FACTOR XI DEFICIENCY (Hemophilia C, Plasma Thromboplastin Antecedent Deficiency, Rosenthal Syndrome)

GENE: F11 (coagulation factor XI)
CHROMOSOMAL LOCATION: 4q35
MUTATIONS ANALYZED: E117X, F283L
CARRIER FREQUENCY: 1 in 8 (Ashkenazi Jewish)
MODE OF INHERITANCE: autosomal recessive

Inherited factor XI (FXI) deficiency, also called Hemophilia C, is an autosomal recessive disorder, which is associated with a variable bleeding tendency that usually manifests after trauma or surgery. Although a rare disorder, the frequency of FXI deficiency is high in certain populations, notably persons of Ashkenazi descent. This assay may be ordered alone or as part of the Ashkenazi Jewish panel. Prenatal testing is available when a mutation is known in the family.

CPT codes:
FACTOR XI DEFICIENCY 83890(1);83891(1);83900(1);83894(1);83892(1);83896(2);83789(2);83912(1)

FAMILIAL ADENOMATOUS POLYPOSIS

GENE: APC (adenomatous polyposis coli)
CHROMOSOMAL LOCATION: 5q21-22
MODE OF INHERITANCE: autosomal dominant

Familial adenomatous polyposis (FAP) is a colon cancer predisposition syndrome in which hundreds to thousands of precancerous colonic polyps develop, beginning at a mean age of 16 years (range 7-36 years). Without colectomy, colon cancer is inevitable. The mean age of colon cancer in untreated individuals is 39 years (range 34-43 years). Extracolonic manifestations may also be present. It has been shown that approximately 20-25% of all FAP cases represent new mutations. Our laboratory offers DNA sequencing of all coding exons (exons 1-15) as well as MLPA analysis for the detection of whole-exon or whole-gene deletions or duplications within APC. These analyses detect up to 90% of mutations in individuals with a clinical diagnosis of FAP.

Prior to testing, we strongly urge all patients to have genetic counseling to review their risk of cancer, to discuss possible findings from screening, and to discuss the relevance of these findings to the management of their health care. Documentation of cancer reported in the family history is advised.

Other phenotypes caused by mutations in APC:
       Attenuated FAP
       Gardner syndrome
       Turcot syndrome

CPT codes:
FAMILIAL ADENOMATOUS POLYPOSIS (APC) (SEQUENCING)
{FAP; FAMILIAL ADENOMATOUS POLYPOSIS; GARDNER SYNDROME}
83890(1);83891(64);83894(2);83898(32);83892(32);83904(64);83909(64);83912(1)

FAMILIAL ADENOMATOUS POLYPOSIS (APC) (MLPA)
{FAP; FAMILIAL ADENOMATOUS POLYPOSIS; GARDNER SYNDROME}
83890(1);83896(36);83898(1);83909(1);83912(1);83914(1)

FAMILIAL ADENOMATOUS POLYPOSIS (APC) (KNOWN MUTATION)
{FAP; FAMILIAL ADENOMATOUS POLYPOSIS; GARDNER SYNDROME}
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

FAMILIAL DYSAUTONOMIA

GENE: IKBKAP (inhibitor of kappa light polypeptide gene enhancer in B cells, kinase complex-associated protein) / IKAP (IKK complex-associated protein)
CHROMOSOMAL LOCATION: 9q31
MUTATIONS ANALYZED: IVS20(+6T->C) and R696P
CARRIER FREQUENCY: 1 in 32 (Ashkenazi Jewish); <1 in 150 (Other) MODE OF INHERITANCE: autosomal recessive

Familial dysautonomia is a progressive neurodegenerative condition that is typically present at birth. Individuals with this condition may have a variety of sensory/neuronal disturbances and a decreased life expectancy. This assay detects greater than 98% of individuals with FD mutations. This assay may be ordered alone or as part of the Ashkenazi Jewish panel. Prenatal testing is available when a mutation is known in the family.

CPT codes:
FAMILIAL DYSAUTONOMIA (2 MUTATIONS)
83890(1);83891(1);83898(2);83894(1);83892(2);83896(2);83789(2);83912(1)

FAMILIAL MEDITERRANEAN FEVER

GENE: MEFV (pyrin)
CHROMOSOMAL LOCATION: 16p13.3
CARRIER FREQUENCY: 1 in 7 (Armenian, Turkish, Arabic); 1 in 28 (Sephardic Jewish)
MODE OF INHERITANCE: autosomal recessive

Familial Mediterranean Fever (FMF) is a genetic disorder characterized by short, recurrent bouts of fever, accompanied by pain in the abdomen, chest, or joints, and an erysipelas-like erythema. The four most common mutations reported to cause FMF and one polymorphism/mutation account for approximately 85% of abnormal alleles in Armenian, Sephardic Jewish, Arabic, or Turkish populations. DNA analysis is recommended for patients who have signs or symptoms suggestive of this disorder to confirm the clinical diagnosis. Direct DNA analysis of the FMF disease gene is also recommended for carrier screening of couples in which at least one person is at high risk. Sequencing of exons 1-10 of the FMF gene is available and detects an estimated 90-95% of all known mutations.

CPT codes:
FAMILIAL MEDITERRANEAN FEVER (5 MUTATIONS)
83890(1);83891(1);83892(5);83894(5);83898(4);83912(1)

FAMILIAL MEDITERRANEAN FEVER (MEFV) (SEQUENCING)
83890(1);83891(20);83894(1);83898(10);83892(10);83904(20);83909(20);83912(1)

FAMILIAL MEDITERRANEAN FEVER (MEFV) (SEQUENCING AFTER 5 COMMON MUTATIONS TESTED)
83894(10);83898(4);83904(12);83912(1)

FAMILIAL MEDITERRANEAN FEVER (MEFV) (KNOWN SEQUENCE MUTATION)
83890(1);83891(1);83894(1);83898(1);83904(2);83909(2);83912(1)

FAMILIAL THORACIC AORTIC ANEURYSMS

GENE: MYH11 (myosin-11)
TGFBR1 (transforming growth factor-beta receptor, type I)
TGFBR2 (transforming growth factor-beta receptor, type II)
FBN1 (fibrillin 1)
CHROMOSOMAL LOCATION: 16p13.13-p13.12 (MYH11); 9q33-34 (TGFBR1); 3p22 (TGFBR2); 15q21.1 (FBN1)
MODE OF INHERITANCE: autosomal dominant

Thoracic aortic aneurysms leading to type A dissections (TAAD) can be inherited in isolation or in association with genetic syndromes, such as Marfan syndrome and Loeys-Dietz syndrome. When TAAD occurs in the absence of syndromic features, it is inherited in an autosomal dominant manner with decreased penetrance and variable expression, the disease is referred to as familial TAAD. Familial TAAD exhibits significant clinical and genetic heterogeneity. Our laboratory offers DNA sequencing of all coding exons and MLPA analysis of the MYH11, TGFBR2, TGFBR1, and FBN1 genes. Of individuals with TAAD, approximately 5-9% have mutations in TGFBR2. In addition, MYH11, TGFBR1, and FBN1 mutations have also been reported in individuals with TAAD. Mutations in MYH11 have been described in individuals with TAAD with patent ductus arteriosus (PDA).

CPT codes:
FAMILIAL THORACIC AORTIC ANEURYSMS (MYH11) (SEQUENCING)
83890(1);83891(82);83892(41);83894(3);83898(41);83904(82);83909(82);83912(1)

FAMILIAL THORACIC AORTIC ANEURYSMS (MYH11) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

FANCONI ANEMIA, TYPE C

GENE: FANCC (fanconi anemia, complementation group C)
CHROMOSOMAL LOCATION: 9q22.3
MUTATION ANALYZED: IVS4+4(A>T)
CARRIER FREQUENCY: 1 in 92 (Ashkenazi Jewish); 1 in 300 (Other)
MODE OF INHERITANCE: autosomal recessive

Individuals with Fanconi Anemia type C typically present with multiple congenital anomalies, followed by pancytopenia in the first decade of life. These individuals are at risk for bone marrow failure and some cancers. DNA mutation analysis is able to detect approximately 83% of individuals with Fanconi Anemia type C. This assay may be ordered alone or as part of the Ashkenazi Jewish panel. Prenatal testing is available when a mutation is known in the family.

CPT codes:
FANCONI ANEMIA TYPE C 83890(1);83891(1); 83898(1);83894(1);83892(1);83896(1);83789(1);83912(1)

FRAGILE X SYNDROME

GENE: FMR1 (fragile X mental retardation 1)
CHROMOSOMAL LOCATION: Xq27.3
INCIDENCE: 1.6-4 in 10,000 affected males; 0.8-2.2 in 10,000 affected females; 1 in 250 carrier females
MODE OF INHERITANCE: X-linked recessive with anticipation

Fragile X syndrome is characterized by moderate mental retardation in affected males and mild mental retardation in affected females. Males may have a characteristic appearance (large head, long face, prominent forehead and chin, protuding ears), connective tissue findings (joint laxity), and large testes (postpubertally). Behavioral abnormalities, sometimes including autism spectrum disorder, are also common. In at least 96% of cases of Fragile-X syndrome there is a trinucleotide repeat expansion (CGG). For most cases, the allele size of one or both (if female) FMR-1 genes is demonstrable by PCR. However, some cases will require a Southern blot analysis to determine allele size and methylation pattern. This assay will be performed automatically if it is necessary. Direct DNA analysis of the FMR-1 gene is recommended for the confirmation of a diagnosis in a patient with or without a family history of the condition. Testing of individuals with a confirmed family history is also possible, as is the prenatal diagnosis of a fetus from a family with a known trinucleotide repeat expansion. Please note that many studies performed for a child who is symptomatic of Fragile-X syndrome have subsequently been found to be negative for Fragile-X and positive for a chromosome abnormality. For this reason we would suggest chromosome analysis concurrently with Fragile-X DNA analysis. About 1 in 250 females are premutation carriers and are at increased risk to develop premature ovarian failure. Male and female premutation carriers are also at risk to develop the Fragile-X Tremor Ataxia Syndrome (FXTAS).

CPT codes:
FRAGILE X (PCR)
83890(1);83891(1);83894(1);83898(1);83912(1)

FRAGILE X (SOUTHERN BLOT)
83892(2);83894(2);83896(2);83897(2);83912(1)

FGF10 RELATED DISORDERS (Lacrimo-Auriculo-Dento-Digital (Levy Hollister); Aplasia of the Lacrimal and Salivary Glands))

GENE: FGF10 (fibroblast growth factor 10)
CHROMOSOMAL LOCATION: 5p13-p12
MODE OF INHERITANCE: autosomal dominant

Mutations in the FGF10 gene have been found in individuals with clinical diagnoses of lacrimo-auriculo-dento-digital (LADD), and aplasia of the lacrimal and salivary glands (ALSG) syndromes. LADD syndrome is characterized by aplasia, atresia or hypoplasia of the lacrimal and salivary systems, cup-shaped ears, hearing loss, and dental and digital anomalies. ALSG syndrome is characterized by xerophthalmia and xerostomia which lead to conjunctival scarring, severe dental caries, dental erosion, and periodontal disease.

Our LADD comprehensive panel includes sequencing of all coding exons and MLPA analysis of the FGF10 gene, sequencing and MLPA analysis of select exons of the FGFR2 gene, as well as sequencing of one exon of the FGFR3 gene. Prenatal testing is available when a mutation is known in the family.

CPT codes:
LADD SYNDROME (FGF10, Selected exons of FGFR2,FGFR3) (SEQUENCING)
83890(1);83891(22);83894(1);83898(11);83892(11);83904(22);83909(22);83912(1)

LADD SYNDROME (MLPA)
83890(1);83898(1);83896(35);83909(1);83914(1);83912(1)

LADD SYNDROME (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

GAUCHER DISEASE

GENE: GBA (acid-beta glucosidase/glucocerebrosidase)
CHROMOSOMAL LOCATION: 1q21-31
MUTATIONS ANALYZED: N370S, 84GG, and L444P
CARRIER FREQUENCY: 1 in 13 (Ashkenazi Jewish); 1 in 150 (Other)
MODE OF INHERITANCE: autosomal recessive

Gaucher disease consists of several subtypes of varying severity that may involve the skeletal, CNS, and cardiopulmonary systems. In almost all cases of Gaucher disease there is a mutation in the gene for glucocerebrosidase. Although over 150 mutations have been identified, three common GD mutations detect approximately 92% of the mutations in the Ashkenazi Jewish population and 55% of the mutations in persons of Non-Ashkenazi Jewish ancestry. The American College of Obstetrics & Gynecology (ACOG) recommends carrier screening for couples in which at least one person is of Ashkenazi Jewish ancestry. DNA analysis is also available for patients who have signs or symptoms suggestive of this disorder. This assay may be ordered alone or as part of the Ashkenazi Jewish panel. Prenatal testing is available when a mutation is known in the family.

CPT codes:
GAUCHER DISEASE
83890(1);83891(1);83900(1);83901(2);83894(1);83892(2);83896(4);83789(4);83912(1)

GLYCOGEN STORAGE DISEASE TYPE 1A (von Gierke Disease)

GENE: G6PC (glucose-6-phosphatase)
CHROMOSOMAL LOCATION: 17q21
MUTATIONS ANALYZED: R83C, Q347X
CARRIER FREQUENCY: 1 in 71 (Ashkenazi Jewish)
MODE OF INHERITANCE: autosomal recessive

GSD1a is a metabolic condition that when untreated, often results in severe hypoglycemia, seizures, hepato- and renomegaly, growth restriction, and bleeding tendencies. The R83C mutation is present in approximately 93-100% of affected individuals of Ashkenazi Jewish descent, and the Q347X mutation is a common mutation observed in individuals of Caucasian descent. This assay may be ordered alone or as part of the Ashkenazi Jewish panel. Prenatal testing is available when a mutation is known in the family.

CPT codes:
GLYCOGEN STORAGE DISEASE 1A (VON GIERKE DISEASE) 83890(1);83891(1);83900(1);83894(1);83892(1);83896(2);83789(2);83912(1)

HEREDITARY HEMOCHROMATOSIS

GENE: HFE
CHROMOSOMAL LOCATION: 6p21.3
INCIDENCE: 1 in 200 to 1 in 400
CARRIER FREQUENCY: 1/7 to 1/10 Caucasians
MODE OF INHERITANCE: autosomal recessive

Hemochromatosis is characterized by inappropriately high absorption of iron by the gastrointestinal mucosa, resulting in excessive storage of iron, particularly in the liver, skin, pancreas, heart, joints, and testes. Abdominal pain, weakness, lethargy, and weight loss are early symptoms. Hereditary hemochromatosis (HHC) may be detected using direct DNA analysis. One mutation (C282Y) and two polymorphisms (H63D, S65C) account for approximately 95% of all hemochromatosis alleles. Testing for HHC is available for the detection of affected persons with or without a family history of this condition. Early detection and presymptomatic diagnosis is important for therapeutic intervention to prevent multi-organ damage from iron overload. DNA mutation analysis is the only reliable method of carrier detection for HHC.

CPT codes:
HEREDITARY HEMOCHROMATOSIS (3 MUTATIONS)
83890(1);83891(1);83892(3);83894(3);83898(2);83912(1)

HEREDITARY HEMOCHROMATOSIS (SINGLE KNOWN MUTATION)
83890(1);83891(1);83892(1);83894(1);83898(1);83912(1)

HUNTINGTON DISEASE

GENE: HTT (huntingtin)
CHROMOSOMAL LOCATION: 4p16.3
INCIDENCE: 3-7 per 100,000 (Western European descent)
MODE OF INHERITANCE: autosomal dominant with anticipation

Huntington disease (HD) is a progressive disorder of motor, cognitive, and psychiatric disturbances. The mean age of onset is 35 to 44 years and the median survival is 15 to 18 years after onset. At least 98% of both familial and sporadic cases of HD have a demonstrable trinucleotide repeat expansion (CAG). Direct DNA analysis of the Huntington disease gene is now recommended for patients without a family history of HD who have signs or symptoms suggestive of this disorder. Predictive testing for presymptomatic patients introduces complex issues and risks. For this reason, pre-test genetic counseling and neurological evaluation are strongly recommended in HD. A signed consent is required to accompany any samples for predictive testing.

CPT codes:
HUNTINGTON DISEASE
83890(1);83891(1);83894(3);83898(3);83912(1)

HUNTINGTON DISEASE XL-PCR (WHEN REQUIRED)
83894(1);83898(1);83912(1)

INFERTILITY TESTING (AZOOSPERMIA DUE TO SPERMATOGENESIS ARREST, INFERTILITY, SUSCEPTIBILITY TO RECURRENT PREGNANCY LOSS)

GENE: SYCP3 (synaptonemal complex protein 3)
CHROMOSOMAL LOCATION: 12q23
MODE OF INHERITANCE: ?autosomal dominant mutations

Spermatogenesis has been shown to arrest in Sycp3-deficient male mice, while Sycp3-deficient female mice have been shown to have an increased risk of intrauterine death due to aneuploid oocytes resulting from defective chromosomal segregation. In human studies, mutations in the SYCP3 gene were first described in two males with non-obstructive azoospermia and consequent infertility, thus implicating SYCP3 as a locus required for completion of spermatogenesis in men. More recently, SYCP3 mutations have been associated with recurrent pregnancy loss in females. Thus, SYCP3 testing may be considered in the workup for women with recurrent pregnancy loss, and in males with non-obstructive azoospermia.
Our laboratory offers DNA sequencing of all coding exons (2-9) of the SYCP3 gene.

CPT codes:
AZOOSPERMIA, MULTIPLE MISCARRIAGES, INFERTILITY (SYCP3) (SEQUENCING)
83890(1);83891(12);83894(1);83898(6);83892(6);83904(12);83909(12);83912(1)

AZOOSPERMIA, MULTIPLE MISCARRIAGES, INFERTILITY (SYCP3) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

JAK2

GENES: JAK2 (janus kinase 2)
CHROMOSOMAL LOCATION: 9p24
REGION ANALYZED: V617F common exon 12 mutation, reflex JAK2 exon 12 sequencing

The acquired Val617Phe (1849G→T) mutation in the JH2 domain within exon 12 of the JAK2 gene occurs in most patients with polycythemia vera, and in approximately half of individuals with essential thrombocythemia and idiopathic myelofibrosis. This mutation has also been seen in patients with myeloid stem disorders including chronic monocytic myeloid leukemia (CMML), acute myeloid leukemia (AML), and myelodysplasia (MDS).

It has recently been discovered that JAK2 exon 12 gain-of-function mutations (non-V617F) occur in patients with a myeloproliferative syndrome who present with erythrocytosis, low serum erythropoietin levels, and a distinctive histologic appearance of the bone marrow.

CPT codes:
JAK2 V617F MUTATION
83890(1);83891(1);83892(1);83894(1);83898(1);83912(1)

JAK2 EXON12 SEQUENCING (REFLEX TEST)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

KENNEDY DISEASE (Spinal Bulbar Muscular Atrophy)

GENE: AR (androgen receptor)
CHROMOSOMAL LOCATION: Xq11-q12
INCIDENCE: 1/50,000
MODE OF INHERITANCE: X-linked

Kennedy Disease, also known as Spinal and Bulbar Muscular Atrophy (SBMA), is a degenerative neuromuscular disorder that affects proximal muscles involved in voluntary activities such as walking, head and neck control and swallowing. SBMA is a rare adult-onset subtype of Spinal Muscular Atrophy. Both familial and sporadic cases of SBMA exhibit a demonstrable trinucleotide repeat expansion (CAG) in exon 1. Direct DNA analysis of the SBMA gene is now recommended for symptomatic patients with or without a family history of the disorder. DNA analysis of patients with a positive family history who do not have signs or symptoms of SBMA is also possible. Predictive testing of these patients, including prenatal diagnosis, introduces complex issues and risks. For this reason we recommend pre-test genetic counseling for SBMA.

CPT codes:
KENNEDY DISEASE (SPINAL BULBAR MUSCULAR ATROPHY)
83890(1);83891(1);83894(1);83898(1);83912(1)

LEOPARD SYNDROME

GENE: PTPN11 (tyrosine-protein phosphatase non-receptor type 11)
RAF1 (RAF proto-oncogene serine/threonine-protein kinase)
CHROMOSOMAL LOCATION: 12q24.1 (PTPN11); 3p25 (RAF1)
MODE OF INHERITANCE: autosomal dominant

LEOPARD syndrome is characterized by multiple lentigines, EKG abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, growth retardation, and sensorineural deafness. There is clinical overlap with features of Noonan syndrome (facial anomalies, distinct congenital heart defects, pectus deformity, hearing loss and short stature). Mutations in the PTPN11 gene have been identified in approximately 90% of patients with the clinical diagnosis of LEOPARD syndrome. Missense mutations in RAF1 are thought to account for approximately 3% of LEOPARD syndrome. Prenatal diagnosis is available when a mutation has been identified in a family.

Testing in LEOPARD syndrome is offered as comprehensive, simultaneous LEOPARD testing of 2 LEOPARD genes (most time effective, with a significantly shorter turn-around-time) or specific testing of any of these genes can be ordered. Once a mutation in the proband is identified, mutation-specific testing in relatives and prenatal diagnosis is available.

CPT codes:
LEOPARD SYNDOME
PTPN11 (SEQUENCING)
83890(1);83891(30);83892(15);83894(1);83898(15);83904(30);83909(30);83912(1)

PTPN11 (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

(RAF1) (SEQUENCING)
83890(1);83891(32);83894(1);83898(16);83892(16);83904(32);83909(32);83912(1)

(RAF1) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

LOEYS-DIETZ SYNDROME

GENE: TGFBR1 (transforming growth factor-beta receptor, type I)
TGFBR2 (transforming growth factor-beta receptor, type II)
CHROMOSOMAL LOCATION: 9q33-34 (TGFBR1); 3p22 (TGFBR2)
MODE OF INHERITANCE: autosomal dominant

Loeys-Dietz syndrome (LDS) is a connective tissue disorder characterized by vascular (dilatation/ dissection of the aorta, arterial aneurysms, tortuosity), skeletal abnormalities, and craniofacial or cutaneous abnormalities. Although patients with LDS may have marfanoid habitus, they typically do not exhibit ectopia lentis or arachnodactyly. Approximately 60% of individuals with a clinical diagnosis of LDS may have a TGFBR2 mutation and about 40% may have a TGFBR1 mutation. Our laboratory offers sequencing of all coding exons (exons 1-9) as well as MLPA analysis for the detection of whole-exon or whole-gene deletions or duplications within TGFBR1. Our laboratory also offers sequencing of all coding exons (exons 1-8) as well as MLPA analysis of select exons for the detection of whole-exon or whole-gene deletions or duplications within TGFBR2. These analyses detect approximately 95% of mutations in individuals with clinically diagnosed Loeys-Dietz syndrome.

MLPA analysis is run concurrently with sequence analysis, however can be performed in a reflex fashion, if specifically requested.

Prenatal diagnosis is available when a mutation has been identified in a family.

Other diseases caused by mutations in TGFBR1:
      Loeys Dietz aortic aneurysm (OMIM# 609192)
      Familial thoracic aortic aneurysms (OMIM# 608967)
      Furlong syndrome (OMIM# 610168)
      Other diseases caused by mutations in TGFBR2:
      Loeys Dietz aortic aneurysm (OMIM# 609192)
      Familial thoracic aortic aneurysms (OMIM# 608967)

CPT codes:
LOEYS-DIETZ SYNDROME (TGFBR1 and TFGBR2) (SEQUENCING both genes)
83890(2);83891(38);83894(2);83898(19);83892(19);83904(38);83909(38);83912(2)

LOEYS-DIETZ SYNDROME (TGFBR1/TGFBR2) (MLPA) both genes
83890(1);83896(32);83898(1);83909(1);83912(1);83914(1)

LOEYS-DIETZ SYNDROME (TGFBR1) (SEQUENCING)
83890(1);83891(18);83892(9);83894(1);83898(9);83904(18);83909(18);83912(1)

LOEYS-DIETZ SYNDROME (TGFBR1) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

LOEYS-DIETZ SYNDROME (TGFBR2) (SEQUENCING)
83890(1);83891(20);83892(10);83894(1);83898(10);83904(20);83909(20);83912(1)

LOEYS-DIETZ SYNDROME (TGFBR2) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

LYNCH SYNDROME/HEREDITARY NON-POLYPOSIS COLORECTAL CANCER (HNPCC)

GENE: MLH1 (DNA mismatch repair protein Mlh1)
MSH2 (DNA mismatch repair protein Msh2)
MSH6 (DNA mismatch repair protein Msh6)
TACSTD1 (Tumor-Associated Calcium Signal Transducer 1)
CHROMOSOMAL LOCATION: 3p21.3 (MLH1); 2p22-p21 (MSH2); 2p16 (MSH6); 2p21 (TACSTD1)
MODE OF INHERITANCE: autosomal dominant

Lynch syndrome/Hereditary non-polyposis colorectal cancer (HNPCC) is a cancer predisposition syndrome caused by mutations in four genes involved in the mismatch repair pathway (MLH1, MSH2, MSH6, and PMS2). In addition, deletions in the TACSTD1 gene may lead to transcriptional interference of the MSH2 gene. Lynch syndrome is thought to account for approximately 1%-3% of colon cancers and 0.8%-1.4% of endometrial cancers. Individuals with Lynch syndrome have an up to 80% lifetime risk for colon cancer, with an average age of diagnosis of 44 years. Women with Lynch syndrome have an up to 20%-60% lifetime risk for endometrial cancer, with an average age of diagnosis of 46 years. Germline mutations in MLH1 and MSH2 account for approximately 90% of detected mutations in families with Lynch syndrome. Mutations in MSH6 have been reported in approximately 7%-10% of families with Lynch syndrome. Our laboratory offers DNA sequencing and MLPA analysis of all coding exons of the MLH1, MSH2, and MSH6 genes. DNA sequence analysis detects approximately 90-95% of Lynch syndrome mutations in the MLH1 gene, 50-80% of Lynch syndrome mutations in the MSH2 gene, and an unknown number of Lynch syndrome mutations in the MSH6 gene. Deletion analysis via MLPA detects approximately 5-10% of mutations in the MLH1 gene, 20-50% of mutations in the MSH2 gene, and an unknown number of mutations in the MSH6 gene. Deletion analysis of exons 3 and 9 via MLPA detects a currently unknown number of mutations in the TACSTD1 gene.

Prior to testing, we strongly urge all patients to have genetic counseling to review their risk of cancer and a hereditary predisposition to cancer based on personal medical history and family history, as well as to discuss the relevance of these findings to the management of their health care. Documentation of cancer reported in the family history is advised.

Other phenotypes caused by mutations in Lynch syndrome genes:
 Muir-Torre syndrome
 Turcot syndrome

CPT codes:
LYNCH SYNDROME/HEREDITARY NON-POLYPOSIS COLORECTAL CANCER (HNPCC) (3 GENES: MSH2, MSH6, MLH1)
CPT codes for complete sequencing and MLPA panel of 3 genes:
83890(1);83891(1);83894(69);83898(69);83904(138);83909(140);83900(1);83901(81);83912(1)

CPT codes by individual gene:
MSH2 (SEQUENCING AND MLPA)
83890(1);83891(1);83894(26);83898(26);83900(1);83901(40);83904(52);83909(52); 83912(1)

MSH6 (SEQUENCING AND MLPA)
83890(1);83891(1);83894(20);83898(20);83900(1);83901(39);83904(40);83909(40); 83912(1)

MLH1 (SEQUENCING AND MLPA)
83890(1);83891(1);83894(23);83898(23);83900(1);83901(40);83904(46);83909(46); 83912(1)

MLH1 and MSH2 (includes TACSTD1) (MLPA ONLY)
83890(1);83891(1);83900(1);83901(40);83909(1);83912(1)

MSH6 (MLPA ONLY)
83890(1);83891(1);83900(1);83901(39);83909(1);83912(1)

KNOWN SEQUENCE MUTATION FOR MSH2, MSH6, or MLH1
83890(1);83891(1);83894(1);83898(1);83904(2);83909(2);83912(1)

MAPLE SYRUP URINE DISEASE TYPE 1B (E1b subunit gene, MSUD type 1B)

GENE: BCKDHB (2-oxoisovalerate dehydrogenase beta subunit)
CHROMOSOMAL LOCATION:6p22-p21
MUTATIONS ANALYZED: G278S, R183P, E372X
CARRIER FREQUENCY: 1 in 81 (Ashkenazi Jewish)
MODE OF INHERITANCE: autosomal recessive

MSUD is a neurodegenerative metabolic condition that when untreated, often results in poor feeding, lethargy, mental retardation, physical disabilities, coma and death. The G278S mutation is typically associated with the intermediate phenotype, while the E372X mutation is typically associated with the classic phenotype. This assay may be ordered alone or as part of the Ashkenazi Jewish panel. Prenatal testing is available when a mutation is known in the family.

CPT codes:
MAPLE SYRUP URINE DISEASE TYPE 1B (BCKDHB)
83890(1);83891(1);83900(1);83901(1);83894(1);83892(2);83896(3);83789(3);83912(1)

MARFAN SYNDROME

GENE: FBN1 (fibrillin 1)
CHROMOSOMAL LOCATION: 15q21.1
MODE OF INHERITANCE: autosomal dominant

Marfan syndrome is a connective tissue disorder that affects multiple organ systems with primary involvement of the skeletal, ocular and cardiovascular systems. A diagnosis is often based on the presence of a family history (75% of individuals have an affected parent) and clinical findings. Up to 90% of individuals with a clinical diagnosis of MFS have FBN1 mutations. Our laboratory offers sequencing of all coding exons (exons 2-66) as well as MLPA analysis for the detection of whole-exon or whole-gene deletions or duplication within FBN1. This analysis detects approximately 70-93% of mutations in patients with a clinical diagnosis of Marfan syndrome.

MLPA analysis is run concurrently with sequence analysis, however can be performed in a reflex fashion, if specifically requested.

Prenatal diagnosis is available when a mutation has been identified in a family.

Individuals who are FBN1 negative, may have a TGFβR2 mutation (up to 21%) or a TGFβR1
mutation (up to 4%). This testing is also available at our Center (see Loeys-Dietz syndrome).

Other conditions caused by mutations in FBN1:
      Shprintzen-Goldberg Craniosynostosis Syndrome (OMIM# 182212)
      Weill-Marchesani Syndrome (OMIM# 608328)
      MASS Syndrome (OMIM# 604328)
      Isolated Ectopia Lentis (OMIM# 129600)
      Familial thoracic aortic aneurysms (OMIM# 608967)

CPT codes:
MARFAN SYNDROME (FBN1) (SEQUENCING)
83890(1);83891(132);83894(4);83898(66);83892(66);83904(132);83909(132);83912(1)

MARFAN SYNDROME (FBN1) (MLPA)
83890(1);83898(1);83896(84);83909(1);83914(1);83912(1)

MARFAN SYNDROME (FBN1) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

MED12 RELATED DISORDERS (FG syndrome type 1 (Opitz-Kaveggia); Lujan-Fryns (X-linked MR with Marfanoid habitus)))

GENE: MED12 (mediator of RNA polymerase II transcription, subunit 12 homolog)
CHROMOSOMAL LOCATION: Xq13
MODE OF INHERITANCE: X-linked

Mutations in the MED12 gene have been found in individuals with clinical diagnoses of FG syndrome (Opitz-Kaveggia) and Lujan-Fryns syndromes. FG syndrome is characterized by typical facial features, mental retardation, macrocephaly, abnormalities of the corpus callosum, imperforate anus, and hypotonia. Individuals with FG syndrome are also thought to have a distinctive behavioral phenotype of hyperactivity and excessive talkativeness. Lujan-Fryns syndrome is characterized by tall stature, thin body habitus, macrocephaly, abnormalities of the corpus callosum, hypernasality, hyperextensible digits, and mental retardation.

Our laboratory offers DNA sequencing of all coding exons (1-45) of the MED12 gene.

This assay may be ordered alone or as part of the X-linked Mental Retardation (XLMR) panel. Prenatal testing is available when a mutation is known in the family.

CPT codes:
FG SYNDROME; LUJAN-FRYNS SYNDROME (MED12) (SEQUENCING)
83890(1);83891(90);83894(3);83898(45);83892(45);83904(90);83909(90);83912(1)

FG SYNDROME; LUJAN-FRYNS SYNDROME) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

MEDIUM-CHAIN ACYL-COA DEHYDROGENASE (MCAD)

GENE: ACADM (medium-chain acyl-CoA dehydrogenase)
CHROMOSOMAL LOCATION: 1p31
INHERITANCE: autosomal recessive

Inherited deficiency of medium-chain acyl-CoA dehydrogenase is characterized by intolerance to prolonged fasting, recurrent episodes of hypoglycemic coma with medium-chain dicarboxylicaciduria, impaired ketogenesis, and low plasma and tissue carnitine levels. The disorder may be severe, and even fatal, in young patients. Our laboratory offers testing for the K304E (985A->G) mutation which accounts for >90% of mutant alleles in the MCAD gene. Approximately 54% of individuals are homozygous for the K304E mutation, and approximately 43% are heterozygous for the K304E mutation and one of 30 rarer alleles.

CPT codes:
MEDIUM-CHAIN ACYL-COA DEHYDROGENASE (MCAD) 1 MUTATION
83890(1);83891(1);83892(1);83894(1);83898(1);83912(1)

MELANOMA (FAMILIAL MALIGNANT) (Dysplastic nevus syndrome)

GENE: CDKN2A (p16: cyclin-dependent kinase inhibitor 2A)
CHROMOSOMAL LOCATION: 9p21
MODE OF INHERITANCE: autosomal dominant

Multiple primary melanomas are not uncommon, however ~10% of melanoma is hereditary. Mutations in the CDKN2A gene are thought to account for up to 40% of hereditary melanoma cases. Individuals with Familial Melanoma have a genetic predisposition to develop multiple clinically abnormal and histologically dysplastic pigmented nevi. Their age at onset tends to be earlier than in individuals with sporadic (non-hereditary) melanoma. Affected individuals also are at increased risk to develop ocular melanoma, and some families show a predisposition to pancreatic cancer. Our laboratory offers sequencing of all coding exons (exons 1-3) as well as MLPA analysis for the detection of whole-exon or whole-gene deletions or duplications within CDKN2A. Prior to testing, we strongly urge all patients to have genetic counseling to review their risk of melanoma, to discuss possible findings from screening, and to discuss the relevance of these findings to the management of their health care. Documentation of cancer reported in the family history is advised.

CPT codes:
FAMILIAL MALIGNANT MELANOMA (CDKN2A) (SEQUENCING)
83890(1);83891(8);83892(4);83894(1);83898(4);83904(8);83909(8);83912(1)

FAMILIAL MALIGNANT MELANOMA (CDKN2A) (MLPA)
83890(1);83896(39);83898(2); 83909(2);83912(1);83914(2)

FAMILIAL MALIGNANT MELANOMA (CDKN2A) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

METHYLENETETRAHYDROFOLATE REDUCTASE (MTHFR)

GENE: MTHFR (methylenetetrahydrofolate reductase)
CHROMOSOMAL LOCATION: 1p36.3
MODE OF INHERITANCE: autosomal recessive

Genetic risk factors are involved in the predisposition of individuals to venous thrombosis. These include increased plasma homocysteine levels, which are associated with a nucleotide variant in the methylenetetrahydrofolate reductase (MTHFR) gene. The MTHFR 677C>T thermolabile variant results in a decreased utilization of folate, which is a cofactor required for homocysteine remethylation. Homozygocity for the MTHFR 677C>T variant is associated with mild to moderate hyperhomocysteinemia. The thrombophilic risk conferred by heterozygosity or homozygosity for the MTHFR 677C>T thermolabile variant remains to be defined. Direct DNA analysis of the MTHFR gene is recommended for all individuals with a family history of venous thrombosis or a known MTHFR variant.

CPT codes:
METHYLENETETRAHYDROFOLATE REDUCTASE (MTHFR)
83890(1);83891(1);83896(2);88299(1);83912(1)

MITOCHONDRIAL DISORDERS

Mitochondrial disorders are a heterogeneous group of diseases that are caused by abnormalities in the mitochondrial respiratory chain. Common clinical features of mitochondrial disease include ptosis, external ophthalmoplegia, proximal myopathy and exercise intolerance, cardiomyopathy, sensorineural deafness, optic atrophy, pigmentary retinopathy, and diabetes mellitus. The central nervous system findings are often fluctuating encephalopathy, seizures, dementia, migraine, stroke-like episodes, ataxia, and spasticity. Mitochondrial disorders may be caused by defects of nuclear DNA or mtDNA. Nuclear gene defects may be inherited in an autosomal dominant or autosomal recessive manner. MtDNA defects are transmitted by maternal inheritance. Many patients display a cluster of clinical features that fall into a specific clinical syndrome; however, there is often considerable clinical variability. Our laboratory offers testing for nine common mutations, including A3243G and T3271C in tRNA-leu (UUR) gene, which cause MELAS (Mitochondrial Encephalopathy, lactic acidosis and stroke-like episodes), A8344G and T8356C in tRNA-lys gene, which cause MERRF (myoclonic epilepsy and ragged red fiber), G3460A, and G11778A mutations, which cause LHON (Lebers hereditary optic neuropathy), and T8993C and T8993G in subunit 6 of ATPase gene, which cause NARP (neuropathy, ataxia and retinitis pigmentosa), which are also responsible for approximately 10% of Leigh syndrome cases. In addition, a common deletion of mtDNA, which causes Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO) or Pearson marrow-pancreas syndrome is also examined. These analyses can be ordered separately or as a panel. In addition, analysis of all 37 mitochondrial genes is now available. Prenatal genetic testing and interpretation of test results for mtDNA disorders are difficult because of mtDNA heteroplasmy.

CPT codes:
MITOCHONDRIAL DISORDERS PANEL (CPEO, KSS, LEIGH SYNDROME, LHON, MELAS, MERRF, NARP)

CPT codes for 9 mutation panel: 83890(1);83891(1);83892(8);83894(9);83898(7);83912(1)

Single mutation analysis (from the 9 common mutations):
83890(1);83891(1);83892(1);83894(1);83898(1);83912(1)

CPT codes by individual disorders:
MITOCHONDRIAL ENCEPHALOPATHY WITH LACTIC ACIDOSIS & STROKE-LIKE EPISODES (MELAS) (2 MUTATIONS)
83890(1);83891(1);83892(2);83894(2);83898(2);83912(1)

KEARNS-SAYRE SYNDROME (KSS/CPEO) (1 MUTATION)
83890(1);83891(1);83894(1);83898(1);83912(1)

LEBER HEREDITARY OPTIC NEUROPATHY (LHON) (2 MUTATIONS)
83890(1);83891(1);83892(2);83894(2);83898(2);83912(1)

MYOCLONIC EPILEPSY WITH RAGGED-RED FIBERS (MERRF) (2 MUTATIONS)
83890(1);83891(1);83892(2);83894(2);83898(2);83912(1)

NEUROPATHY WITH ATAXIA & RETINITIS PIGMENTOSA (NARP) (2 MUTATIONS)/
LEIGH SYNDROME (MITOCHONDRIAL) (2 MUTATIONS)
83890(1);83891(1);83892(2);83894(2);83898(2);83912(1)

MITOCHONDRIAL GENOME ANALYSIS (SEQUENCE ANALYSIS OF ALL 37 GENES)
83890(1);83891(1);83892(1);83894(3);83896(348);83898(3);83912(1)

MITOCHONDRIAL SINGLE MUTATION ANALYSIS (KNOWN SEQUENCE MUTATION)
83890(1);83891(1);83892(1);83894(1);83898(1);83912(1)

MUCOLIPIDOSIS TYPE IV

GENE: MCOLN1 (mucolipin-1)
CHROMOSOMAL LOCATION:19p13.3-p13.2
MUTATIONS ANALYZED: IVS3-2 A>G, Deletion exons 1-7
CARRIER FREQUENCY: 1 in 122 (Ashkenazi Jewish)
MODE OF INHERITANCE: autosomal recessive

Mucolipidosis type IV is a neurodegenerative lysosomal storage disorder characterized clinically by severe psychomotor retardation and ophthalmologic abnormalities. The splice mutation and partial gene deletion account for approximately 95% of mutations in individuals with Ashkenazi Jewish descent. This assay may be ordered alone or as part of the Ashkenazi Jewish panel. Prenatal testing is available when a mutation is known in the family.

CPT codes:
MUCOLIPIDOSIS TYPE IV (MCOLN1)
83890(1);83891(1);83900(1);83894(2);83898(1);83892(1);83896(1);83789(1);83912(1)

MYH-ASSOCIATED POLYPOSIS (MAP)

GENE: MUTYH (mutY (E. coli) homolog)
CHROMOSOMAL LOCATION: 1p34.3-32.1
MODE OF INHERITANCE: autosomal recessive

Individuals with MYH-Associated Polyposis (MAP) have a wide range of numbers of colon polyps, some having less severe polyposis (as in attenuated FAP) and some appearing more like FAP with hundreds of polyps. Due to the autosomal recessive pattern of inheritance, patients with MAP often have no family history of colon cancer or polyps. Our laboratory offers DNA sequencing of all coding exons (exons 1-16) as well as MLPA analysis of select exons for the detection of whole-exon or whole-gene deletions or duplications within MUTYH.

Prior to testing, we strongly urge all patients to have genetic counseling to review their risk of colon cancer, to discuss possible findings from screening, and to discuss the relevance of these findings to the management of their health care. Documentation of cancer reported in the family history is advised.

CPT codes:
MYH-ASSOCIATED POLYPOSIS (MAP) (MUTYH) (SEQUENCING)
83890(1);83891(32);83892(16);83894(1);83898(16);83904(32);83909(32);83912(1)

MYH-ASSOCIATED POLYPOSIS (MAP) (MUTYH) (MLPA)
83890(1);83896(39);83898(1);83914(1);83909(1);83912(1)

MYH-ASSOCIATED POLYPOSIS (MAP) (MUTYH) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

NEUROFIBROMATOSIS 1

GENE: NF1 (neurofibromin)
CHROMOSOMAL LOCATION: 17q11.2
MODE OF INHERITANCE: autosomal dominant

Neurofibromatosis 1 (NF1) is characterized by multiple café au lait macules, axillary and inguinal freckling, neurofibromas, and iris Lisch nodules. Learning disabilities are present in at least 50% of individuals with Neurofibromatosis 1. Our laboratory offers DNA sequencing of all coding exons (exons 1-58) as well as MLPA analysis of select exons for the detection of whole-exon or whole-gene deletions or duplications within NF1. These analyses detect approximately 90-95% of mutations in individuals with a clinical diagnosis of Neurofibromatosis 1. Prenatal diagnosis is available when a mutation has been identified in a family.

CPT codes:
NEUROFIBROMATOSIS TYPE 1 (NF1) (SEQUENCING)
83890(1);83891(122);83894(4);83898(61);83892(61);83904(122);83909(122);83912(1)

NEUROFIBROMATOSIS TYPE 1 (NF1) (MLPA)
83890(1);83898(2);83896(80);83909(2);83914(2);83912(1)

NEUROFIBROMATOSIS TYPE 1 (NF1) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

NEUROFIBROMATOSIS TYPE 1-LIKE SYNDROME (NFLS)

GENE: SPRED1 (sprouty-related, EVH1 domain containing 1)
CHROMOSOMAL LOCATION: 15q14
MODE OF INHERITANCE: autosomal dominant

SPRED1 gene mutations have recently been described in multiple patients with a Neurofibromatosis type 1-like syndrome. The phenotype associated with NFLS consists of multiple café-au-lait macules, axillary freckling, and macrocephaly. Some patients also have learning disabilities. It is estimated that up to 3% of individuals with a clinical diagnosis of NF1 have NFLS.

Sequencing of the SPRED1 gene should be considered in patients with no detectable NF1 mutation.
Our laboratory offers DNA sequencing of all coding exons (2-8) of the SPRED1 gene. Prenatal testing is available when a mutation is known in the family.

CPT codes:
NEUROFIBROMATOSIS TYPE 1-LIKE SYNDROME (SPRED1) (SEQUENCING)
83890(1);83891(16);83894(1);83898(8);83892(8);83904(16);83909(16);83912(1)

NEUROFIBROMATOSIS TYPE 1-LIKE SYNDROME (SPRED1) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

NEUROFIBROMATOSIS 2

GENE: NF2 (merlin)
CHROMOSOMAL LOCATION: 22q12.2
MODE OF INHERITANCE: autosomal dominant

Neurofibromatosis 2 (NF2) is characterized by bilateral vestibular schwannomas. Posterior subcapsular lens cataracts are also common features. Our laboratory offers sequencing of all coding exons (exons 1-17) as well as MLPA analysis for the detection of whole-exon or whole-gene deletions or duplications within NF2. These analyses detect approximately 90% of mutations in individuals with a clinical diagnosis of Neurofibromatosis 2. Prenatal diagnosis is available when a mutation has been identified in a family.

CPT codes:
NEUROFIBROMATOSIS TYPE 2 (NF2) (SEQUENCING)
83890(1);83891(34);83894(1);83898(17);83892(17);83904(34);83909(34);83912(1)

NEUROFIBROMATOSIS TYPE 2 (NF2) (MLPA)
83890(1);83898(2);83896(33);83909(2);83914(2);83912(1)

NEUROFIBROMATOSIS TYPE 2 (NF2) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

NEUROLIGIN (X-LINKED MENTAL RETARDATION/AUTISM/ASPERGER SYNDROME)
GENE: NGLN3 and NGLN4
CHROMOSOMAL LOCATION: Xq13 and Xp22
MODE OF INHERITANCE: X-linked recessive

Mutations in either of these two X-linked genes have been described in Autism/PDD/Asperger syndrome and non-specific mental retardation in males.

CPT codes:
NEUROLIGIN (X-LINKED MENTAL RETARDATION/AUTISM/ASPERGER SYNDROME)
NLGN3 (SEQUENCING)
83890(1);83891(1);83894(6);83898(6);83904(16);83909(16);83912(1)

NLGN3 (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

NLGN4 (SEQUENCING)
83890(1);83891(1);83894(5);83898(5);83904(20);83909(20);83912(1)

NLGN4 (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

NIEMANN PICK DISEASE, TYPE A

GENE: SMPD1 (acid sphingomyelinase (ASM)/sphingomyelin phosphodiesterase-1)
CHROMOSOMAL LOCATION: 11p15.4-p15.1
MUTATIONS ANALYZED: R496L, L302P, and fsP330
CARRIER FREQUENCY: 1 in 90 (Ashkenazi Jewish)
MODE OF INHERITANCE: autosomal recessive

Niemann-Pick disease (type A) is the most common and most severe subtype of NPD. Patients with NPDA typically have less than 5% of normal acid sphingomyelinase levels, which leads to severe neurological disease in infancy and early childhood. Three mutations in the SMPD1 gene account for approximately 94% of all cases of NPDA. This assay may be ordered alone or as part of the Ashkenazi Jewish panel. Prenatal testing is available when a mutation is known in the family.

CPT codes:
NIEMANN-PICK DISEASE TYPE A (3 MUTATIONS)
83890(1);83891(1);83900(1);83901(1);83894(1);83892(1);83896(3);83789(3);83912(1)

NOONAN SYNDROME

GENE: PTPN11 (tyrosine-protein phosphatase non-receptor type 11)
SOS1 (son of sevenless homolog 1)
RAF1 (RAF proto-oncogene serine/threonine-protein kinase)
KRAS (GTPase KRas)
SHOC2 (soc-2 suppressor of clear homolog)

CHROMOSOMAL LOCATION: 12q24.1 (PTPN11); 3p25 (RAF1); 2p22-p21 (SOS1); 12p12.1 (KRAS); 10q25 (SHOC2)

MODE OF INHERITANCE: autosomal dominant

Noonan syndrome is characterized by short stature, distinct facial features, congenital heart disease, and developmental delay/mental retardation. Noonan syndrome is genetically heterogeneous. Our laboratory offers DNA sequencing of all coding exons of the PTPN11, RAF1, SOS1, and KRAS genes, as well as single mutation analysis (S2G) within the SHOC2 gene. Missense mutations in the PTPN11 gene have been detected in approximately 50% of individuals with a clinical diagnosis of Noonan syndrome. Mutations in the RAF1, SOS1, and KRAS genes have been observed in 3-17%, 10-13%, and <5%%, respectively. Recently, the S2G SHOC2 mutation has been observed in 4-5% of patients with Noonan syndrome, particularly with loose anagen hair. Testing in Noonan syndrome is offered as comprehensive, simultaneous Noonan testing of all 5 Noonan genes (most time effective, with a significantly shorter turn-around-time) or specific testing of any of these genes can be ordered. Once a mutation in the proband is identified, mutation-specific testing in relatives and prenatal diagnosis is available.

Other indications for Noonan syndrome testing:
Our laboratory offers sequencing of PTPN11, RAF1, SOS1, KRAS, as well as S2G SHOC2 mutation analysis for fetuses with an increased nuchal translucency or cystic hygroma detected on fetal ultrasound.

CPT codes:
NOONAN SYNDROME
Complete panel includes sequence analysis of PTPN11, SOS1, KRAS, and RAF1 and SHOC2 mutation analysis
CPT codes for set of 4 genes (PTPN11;SOS1;KRAS;SHOC2)
83890(1);83891(122);83894(5);83898(62);83892(62);83904(122);83909(122);83912(1)

CPT codes for RAF1
83890(1);83891(32);83894(1);83898(16);83892(16);83904(32);83909(32);83912(1)

CPT codes for individual genes:
PTPN11 (SEQUENCING)
83890(1);83891(30);83892(15);83894(1);83898(15);83904(30);83909(30);83912(1)

PTPN11 (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

SOS1 (SEQUENCING)
83890(1);83891(50);83892(25);83894(1);83898(25);83904(50);83909(50);83912(1)

SOS1 (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

KRAS (SEQUENCING)
83890(1);83891(10);83892(5);83894(1);83898(5);83904(10);83909(10);83912(1)

KRAS (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

RAF1 (SEQUENCING)
83890(1);83891(32);83894(1);83898(16);83892(16);83904(32);83909(32);83912(1)

RAF1 (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

SHOC2 (SPECIFIC MUTATION S2G)
83890(1);83891(1);83892(1);83894(1);83898(1);83912(1)

OPITZ G/BBB SYNDROME (X-LINKED)

GENE: MID1 (midline-1)
CHROMOSOMAL LOCATION: Xp22
MODE OF INHERITANCE: X-linked

X-linked Opitz G/BBB syndrome is a multiple congenital anomaly disorder characterized by characteristic facial anomalies (ocular hypertelorism, prominent forehead, widow’s peak, anteverted nares), cleft lip and/or palate, genitourinary abnormalities, and developmental delay/mental retardation. Female carriers typically only manifest ocular hypertelorism. Our laboratory offers DNA sequencing of all coding exons (exons 2-10) as well as MLPA analysis for the detection of whole-exon or whole-gene deletions or duplications within MID1. MID1 is the only gene known to be associated with X-linked Opitz G/BBB syndrome. This analysis detects up to 45% of mutations in males with clinically diagnosed Opitz G/BBB syndrome.

This assay may be ordered alone or as part of the X-linked Mental Retardation (XLMR) panel. Prenatal testing is available when a mutation is known in the family.

CPT codes:
X-LINKED OPITZ G/BBB SYNDROME (MID1) (SEQUENCING)
83890(1);83891(20);83892(10);83894(1);83898(10);83904(20);83909(20);83912(1)

X-LINKED OPITZ G/BBB SYNDROME (MID1) (MLPA)
83890(1);83896(23);83898(1);83909(1);83914(23);83912(1)

X-LINKED OPITZ G/BBB SYNDROME (MID1) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

PARAGANGLIOMA

GENE: SDHD (succinate dehydrogenase complex, subunit D)
CHROMOSOMAL LOCATION: 11q23
MODE OF INHERITANCE: autosomal dominant, with imprinting

Familial paragangliomas (PGL), or glomus tumors, are slow-growing, highly vascular, generally benign neoplasms usually of the head and neck that arise from neural crest cells. Pheochromocytomas may also occur. This rare autosomal-dominant disorder is highly penetrant and influenced by genomic imprinting through paternal transmission. Our laboratory offers DNA sequencing for the identification of mutations in this gene. Timely detection of tumors in those predicted to be affected affords the affected individual the opportunity to avoid the potential morbidity associated with surgical removal, and mortality that may accompany local and distant metastases.

CPT codes:
PARAGANGLIOMA (SDHD) (SEQUENCING)
83890(1);83891(1);83894(8);83898(4);83904(8);83912(1)

PARAGANGLIOMA (SDHD) (KNOWN MUTATION)
83890(1);83891(1);83894(2);83898(1);83904(2);83912(1)

PATERNITY DNA ANALYSIS

We offer DNA analysis testing to determine paternity. This test requires a blood sample from the potential father(s) and the child(ren). A blood sample from the mother is optional. Fetuses can be tested by routine fetal sampling procedures (i.e., chorionic villus sampling or amniocentesis), or from cord blood at the time of birth. The accuracy of paternity DNA analysis is 100% if the potential father is excluded as the biological father of the child. If the potential father is included as the biological father of the child the accuracy is greater than 99.9%. This is the required certainty for a court of law. Interested individuals in the Boston area may call for an appointment to have their blood samples drawn at the Center for Human Genetics. Please note that we will require photo identification from adults and photographs will be taken of minors without photo identification. In addition, cheek swabs are available for young children and babies in lieu of a blood sample. The accuracy remains the same. Our laboratory can also accept samples drawn at outside institutions. Please call prior to drawing samples so that we can send you the appropriate legal forms to complete and send with the samples. Results can be expected in 4-6 weeks. The cost of testing is generally not covered by any insurance company and must be paid in full the time the samples are submitted. Cash, credit card, certified check, or money order are acceptable forms of payment.

PELIZAEUS-MERZBACHER DISEASE/ SPASTIC PARAPLEGIA 2

GENE: PLP1 (myelin proteolipid protein 1)
CHROMOSOMAL LOCATION: Xq22
MODE OF INHERITANCE: X-linked

Pelizaeus-Merzbacher disease is a neurodegenerative disorder that affects primarily the white matter of the central nervous system. The condition typically presents in infancy or early childhood and is characterized by nystagmus, impaired motor development, ataxia, choreoathetotic movements, dysarthria, and progressive spasticity. Spastic paraplegia 2 often presents with spastic paraparesis with or without CNS involvement. Our laboratory offers MLPA analysis of all coding exons for the detection of whole-exon or whole-gene deletions or duplications within PLP1. Duplication of PLP1 is the most frequent mutation found in approximately 50%-75% of PMD patients, and deletions have been reported in <2% of patients. Additionally, our laboratory offers DNA sequence analysis of all coding exons of the PLP1 gene. Point mutations in PLP1 are present in approximately 15%-25% of patients.
These assays are performed concurrently, unless specifically requested to be performed in a sequential manner.

This assay may be ordered alone or as part of the X-linked Mental Retardation (XLMR) panel. Prenatal testing is available when a mutation is known in the family.

CPT codes:
PELIZAEUS-MERZBACHER DISEASE/SPASTIC PARAPLEGIA 2 (PLP1) (SEQUENCING)
83890(1);83891(14);83892(7);83894(1);83898(7);83904(14);83909(14);83912(1)

PELIZAEUS-MERZBACHER DISEASE/SPASTIC PARAPLEGIA 2 (PLP1) (MLPA)
83890(1);83896(31);83898(1);83914(1);83909(1);83912(1)

PELIZAEUS-MERZBACHER DISEASE/SPASTIC PARAPLEGIA 2 (PLP1) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

PENDRED SYNDROME

GENE: SLC26A4 (solute carrier family 26, member 4) / Pendrin
CHROMOSOMAL LOCATION: 7q31
INHERITANCE: autosomal recessive

Pendred syndrome is one of the most common syndromic forms of deafness. It is an autosomal recessive disorder associated with developmental abnormalities of the cochlea (Mondini dysplasia), sensorineural hearing loss, and diffuse thyroid enlargement (goiter). It is caused by mutations in the SLC26A4 gene. Our laboratory offers testing for the L236P, IVS 8+1, E384G, T416P, and FS400 Pendred mutations. This analysis detects up to 60% of all reported mutations in the SLC26A4 gene known to cause Pendred syndrome. Mutations in this gene also cause non-syndromic deafness mapping to 7q31 (DFNB4) as well as enlarged vestibular aqueduct syndrome (EVA)/Mondini dysplasia.

CPT codes:
PENDRED SYNDROME (5 COMMON MUTATIONS)
83890(1);83891(1);83892(5);83894(5);83898(5);83912(1)

PHENYLKETONURIA (PKU)

GENE: PAH (phenylalanine hydroxylase)
CHROMOSOMAL LOCATION: 12q32.2
MODE OF INHERITANCE: autosomal recessive

Phenylketonuria (PKU) is caused by a deficiency in phenyalanine hydroxylase which results in intolerance to the dietary intake of the essential amino acid phenylalanine. Without dietary restriction of phenylalanine, most children with PKU develop profound and irreversible mental retardation. Our laboratory offers DNA sequencing of all coding exons (exons 1-13) as well as MLPA analysis for the detection of whole-exon or whole-gene deletions or duplications within PAH. Together, these analyses are thought to detect approximately 99% of mutations in PAH.

Prenatal testing is available when the mutations are known in the family.

CPT codes:
PHENYLKETONURIA (PKU; PAH) (SEQUENCING)
83890(1);83891(26);83892(13);83894(1);83898(13);83904(26);83909(26);83912(1)

PHENYLKETONURIA (PKU; PAH) (MLPA)
83890(1);83896(25);83898(1);83909(1);83912(1);83914(1)

PHENYLKETONURIA (PKU; PAH) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

PRADER-WILLI SYNDROME

GENE: SNRPN
CHROMOSOMAL LOCATION: 15q11
INCIDENCE: 1 in 25,000 births
MODE OF INHERITANCE: deletion; uniparental disomy; imprinting defects; some autosomal dominant rearrangements

Prader-Willi syndrome is characterized by severe hypotonia and feeding difficulties in early infancy, followed by excessive eating and gradual development of morbid obesity (unless externally controlled) in later infancy and childhood. All patients have some degree of cognitive impairment. Hypogonadism, short stature, and characteristic behaviors are also common. Prader-Willi syndrome (PWS) is caused by a deletion or disruption of the paternal SNRPN gene region. Our methylation-sensitive assay detects both deletions of the paternal chromosome 15 and uniparental disomy of the maternal chromosome 15. Approximately 98% of PWS cases are detectable using this assay. This direct DNA analysis for PWS is now recommended for the confirmation of a diagnosis in a patient with or without a family history of the condition. Karyotyping parents of an affected child and methylation studies of a fetus are available for prenatal diagnosis. Further studies, including FISH deletion analysis and uniparental disomy studies (which require parental blood samples), are available and recommended following a positive test result.

CPT codes:
PRADER-WILLI SYNDROME
83890(1);83891(1);83892(1);83894(1);83896(1);83897(1);83912(1)

PROTHROMBIN

GENE: F2 (coagulation factor II)
CHROMOSOMAL LOCATION: 11p11-q12
INCIDENCE: 1-2% of the Caucasian population
MODE OF INHERITANCE: autosomal dominant

Prothrombin is the precursor of thrombin (the activated form of factor II) in the clotting cascade. A mutation in the gene for prothrombin causes an elevation of the level of functional prothrombin in plasma, which is associated with an increased risk of thrombosis. Persons who are at risk to carry the prothrombin mutation are those with a family history of early onset stroke, deep vein thrombosis, thromboembolism, pregnancy associated with thrombosis/embolism, hyperhomocystinemia, and multiple miscarriage. Individuals with the mutation are at increased risk of thrombosis in the setting of oral contraceptive use, trauma, and surgery. Direct DNA analysis of the Factor V (see above) and prothrombin mutations are now recommended for at-risk patients because of the importance of therapy and antithrombotic prophylaxis.

CPT codes:
PROTHROMBIN GENE MUTATION (20210G>A)
83890(1);83891(1);83896(2);88299(1);83912(1)

PTEN-HAMARTOMA TUMOR SYNDROME (Cowden, Bannayan-Riley-Ruvalcaba, Proteus/Proteus-Like; Autism with macrocephaly)

GENE: PTEN (phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase)
CHROMOSOMAL LOCATION: 10q23.3
MODE OF INHERITANCE: autosomal dominant

The PTEN-hamartoma tumor syndrome (PHTS) includes Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Proteus-like syndrome. This group of disorders shares significant clinical overlap, most notably predisposition to hamartomatous polyposis of the GI tract. Cowden syndrome is characterized by increased risk for both benign and malignant tumors of the breast, thyroid, and endometrium. Affected individuals have macrocephaly and almost all will develop mucocutaneous lesions including trichilemmomas, papillomatous papules, and acral and plantar keratoses. Bannayan-Riley-Ruvalcaba syndrome is a congenital disorder characterized by macrocephaly, intestinal polyposis, lipomas, and enlargement and spotty pigmentation of the glans penis. Proteus and Proteus-like syndromes are congenital disorders with hamartomatous overgrowth of any tissue. Our laboratory offers DNA sequencing of the promoter region, all coding exons, as well as MLPA analysis of the PTEN gene. Sequence analysis of the PTEN gene detects mutations in approximately 80% of individuals with a clinical diagnosis of Cowden syndrome, 60% of individuals with a clinical diagnosis of Bannayan-Riley-Ruvalcaba syndrome, 50% of individuals with a clinical diagnosis of Proteus-like syndrome, and 20% individuals with a clinical diagnosis of Proteus syndrome. Deletions in PTEN are thought to account for approximately 10% of individuals with a clinical diagnosis of Bannayan-Riley-Ruvalcaba syndrome. Sequencing of the promoter region of PTEN detects mutations that alter gene function in approximately 10% of individuals with a clinical diagnosis of Cowden syndrome who do not have an identifiable mutation in the PTEN coding region.
Prenatal testing is available when a mutation has been identified in a family.
Other phenotypes caused by mutations in PTEN:
 Adult onset Lhermitte-Duclos disease
 Patients with autism spectrum disorder and macrocephaly

Autism spectrum disorders are a group of neurodevelopmental disorders, in which patients show deficits in social interaction, impaired communication, repetitive behavior and restricted interests and activities. It is reported that 25-30% of patients with autism spectrum disorders have a head circumference greater than the 98th percentile. It is reported that 20% of individuals with autism spectrum disorders and macrocephaly have PTEN mutations.

CPT codes:
PTEN-HAMARTOMA TUMOR SYNDROME (Cowden, Bannayan-Riley-Ruvalcaba, Proteus/Proteus-Like; Autism with macrocephaly)
(PTEN) (SEQUENCING)
83890(1);83891(18);83892(9);83894(1);83898(9);83904(18);83909(18);83912(1)

(PTEN) (MLPA)
83890(1);83896(46);83898(2);83909(2);83914(2);83912(1)

(PTEN PROMOTER TEST)
83891(4);83892(2);83894(1);83898(2);83904(4);83909(4);83912(1)

(PTEN) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

RETT SYNDROME

GENE: MECP2 (methyl-CpG-binding protein 2)
CHROMOSOMAL LOCATION: Xp11
MODE OF INHERITANCE: X-linked

Rett syndrome is a progressive neurological disorder in which individuals exhibit reduced muscle tone, autistic-like behavior, microcephaly, wringing and flapping hand movements, loss of purposeful use of the hands, diminished ability to express feelings, avoidance of eye contact, a lag in brain and head growth, gait abnormalities, and seizures. Symptoms typically occur between ages 6 and 18 months. Our laboratory offers DNA sequencing of MECP2 for the identification of mutations in this gene. Sequencing of exons 1-4 will detect approximately 80% of patients with Rett syndrome. MLPA analysis will detect an additional 10-12% of individuals with classic Rett syndrome who have a large deletion or duplication, not detectable by routine sequencing analysis. Prenatal diagnosis is available when the MECP2 mutation has been identified in a family.

Other phenotypes caused by mutations in MECP2:
      Males with X-linked mental retardation and spasticity (OMIM# 300055)
      Males with X-linked mental retardation, Lubs type (OMIM# 300260)
      Males with neonatal-onset encephalopathy (OMIM# 300673)
      Females with Angelman-like phenotype
      Males with PPM-X (psychosis, pyramidal signs, and macroorchidism)
      Preserved-speech variant Rett syndrome
      “Forme-fruste” Rett syndrome

CPT codes:
RETT SYNDROME (MECP2) (SEQUENCING AND MLPA)
83890(1);83891(1);83894(11);83898(10);83900(1);83901(27);83904(5);83909(1);83912(1)

RETT SYNDROME (MECP2) (MLPA ONLY)
83890(1);83896(27);83898(1);83914(1);83909(1);83912(1)

RETT SYNDROME (MECP2) (KNOWN MUTATION)
83890(1);83891(1);83894(2);83898(2);83904(2);83912(1)

RETT SYNDROME – ATYPICAL

GENE: CDKL5/STK9 (cyclin-dependent kinase-like 5; serine/threonine protein kinase 9)
CHROMOSOMAL LOCATION: Xp22
MODE OF INHERITANCE: X-linked

Mutations in the CDKL5 gene (also known as STK9) has been associated with an atypical variant of Rett syndrome, with severe early-onset seizures or infantile spasms, loss of communication and motor skills, and severe mental retardation . The CDKL5 associated phenotype may be severe, with early-onset encephalopathy, infantile spasms, severe global developmental delay, and profound intellectual impairment seen in female and male patients. At the mild end of the spectrum are patients with mild mental retardation with autistic features. Many of these clinical features meet the criteria for the early-onset variant of Rett syndrome.
Our laboratory offers DNA sequencing of all coding exons (exons 2-21) as well as MLPA analysis for the detection of whole-exon or whole-gene deletions or duplications within CDKL5. Prenatal diagnosis is available when a mutation has been identified in a family.

Patients who previously tested negative for comprehensive mutation analysis in the MECP2 gene are candidates for CDKL5 sequence analysis.

Other phenotypes caused by mutations in CDKL5:
 Females with West syndrome (infantile spasms, hypsarrhythmia, and mental retardation

CPT codes:
RETT SYNDROME – ATYPICAL (STK9; CDKL5) (SEQUENCING)
83890(1);83891(44);83894(22);83898(66);83904(44);83909(44);83912(1)

RETT SYNDROME – ATYPICAL (STK9; CDKL5) (MLPA)
83890(1);83896(46);83898(1);83914(1);83909(1);83912(1)

RETT SYNDROME – ATYPICAL (STK9; CDKL5) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

SICKLE CELL ANEMIA

GENE: hemoglobin beta (HBB)
CHROMOSOMAL LOCATION: 11p
CARRIER FREQUENCY: 1 in 10 African-Americans
MODE OF INHERITANCE: autosomal recessive

Sickle cell disease is characterized by variable degrees of hemolysis and intermittent episodes of vascular occlusion resulting in tissue ischemia and acute and chronic organ dysfunction. Resulting complications include anemia, jaundice, predisposition to aplastic crisis, sepsis, cholelithiasis, and delayed growth. The change in the beta globin gene that causes sickle-cell anemia has been well described. Our assay differentiates beta globin A, S, and C. Thus we are able to detect sickle-cell anemia, SC disease, “sickle trait” (carriers of the S allele), and “C trait” (carriers of the C allele). Direct DNA analysis of the beta globin gene is available for prenatal diagnosis when both parents are known or suspected carriers.

CPT codes:
SICKLE CELL ANEMIA
83890(1);83891(1);83892(2);83894(2);83898(1);83912(1)

SLC16A2-SPECIFIC THYROID HORMONE CELL TRANSPORTER DEFICIENCY (Allan-Herndon-Dudley, Triiodothyronine resistance, X-linked MR with hypotonia)

GENE: MCT8/ SLC16A2 (solute carrier family 16 (monocarboxylic acid transporters), member 2
CHROMOSOMAL LOCATION: Xq13.2
MODE OF INHERITANCE: X-linked

Mutations in the MCT8/SLC16A2 gene are associated with mental retardation, impaired speech, and congenital hypotonia with eventual spasticity. The MCT8/SLC16A2 gene is important for the neuronal uptake of triiodothyronine (T3) in its function as a specific and active transporter of thyroid hormones across the cell membrane. Therefore, mutations in MCT8/SLC16A2 typically cause elevated serum levels of free T3, and low-normal serum levels of free T4. Levels of TSH are typically within the normal range.
Our laboratory offers DNA sequencing of all coding exons (1-6) of the MCT8/SLC16A2 gene.
This assay may be ordered alone or as part of the X-linked Mental Retardation (XLMR) panel. Prenatal testing is available when a mutation is known in the family.

CPT codes:
ALLAN-HERNDON-DUDLEY SYNDROME (SLC16A2) (SEQUENCING)
83890(1);83891(16);83894(1);83898(8);83892(8);83904(16);83909(16);83912(1)

ALLAN-HERNDON-DUDLEY SYNDROME (SLC16A2) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

SMITH-LEMLI-OPITZ SYNDROME (SLO)

GENE: DHCR7 (7-dehydrocholesterol reductase)
CHROMOSOMAL LOCATION: 11q12-q13
CARRIER FREQUENCY: 1 in 100 individuals
MODE OF INHERITANCE: autosomal recessive

Smith-Lemli-Opitz is characterized by failure to thrive, microcephaly, developmental delay, ptosis, hypospadias, dysmorphic features, syndactyly, low total cholesterol and elevated 7-dehydrocholesterol. Sequence analysis of 7 exons of the SLO gene, which detects up to 90% of all known mutations. Prenatal diagnosis is available when the DHCR7 mutations have been identified in the family.

CPT codes:
SMITH-LEMLI-OPITZ SEQUENCING (DHCR7) (SEQUENCING)
83890(1);83891(1);83894(15);83898(7);83904(16);83912(1)

SMITH-LEMLI-OPITZ (DHCR7) (KNOWN MUTATION)
83890(1);83891(1);83894(2);83898(2);83904(2);83912(1)

SNP MICROARRAY (6.0)

6.0 DNA-SNP MICROARRAY
IMPORTANT NEW DNA TEST FOR UNEXPLAINED MENTAL RETARDATION, AUTISM, AND/OR CONGENITAL MALFORMATIONS

This new test enables analysis of 1.8 million copy number probes/single nucleotide bases (termed SNPs – single nucleotide polymorphisms) distributed throughout the human genome, facilitating detection of microdeletions or microduplications of 50 or more SNPs (termed CNV – copy number variants).

SCOPE: This test will detect:
1. All microdeletions/microduplications throughout the genome including many known syndromes.
2. All numerical chromosome abnormalities including trisomies, monosomies, unbalanced translocations, mosaicism and supernumerary (marker) chromosomes.

BENEFIT: This new advance is valuable and important and WILL:
1. Enable recognition of significant and often unexpected microdeletions/duplications throughout the genome (Y- chromosome excluded). The coverage is MORE EXTENSIVE AND LESS EXPENSIVE THAN ANY OTHER EQUALLY COMPREHENSIVE AVAILABLE MICROARRAY.
2. Recognize microdeletions/duplications not determinable by gene sequencing and be valuable in detecting these abnormalities in about 10% of those with autism.
3. Add a 10-20% detection rate to the diagnosis of unexplained mental retardation/congenital malformations after negative results on karyotyping.
4. Not only target specific disorders, as in other microarrays, but cover the genome including subtelomeric regions, supplemented by an additional assay at no extra cost.
5. Be valuable in those individuals with mental retardation and/or anomalies who have previously been determined to have “balanced chromosome rearrangements”.
6. No longer require separate assays for routine comparative genomic hybridization or subtelomeric chromosome analysis.
7. Recognize uniparental disomy for any autosomal chromosome pair (when specifically ordered).

LIMITATIONS:
1. The samples are analyzed at a resolution of 50 Kb for the known microdeletion/duplication syndromes and subtelomeric regions. The remaining genome is analyzed at a resolution of 200 Kb (deletions less than 200 Kb and duplications less than 500 Kb are not reported).
2. Balanced structural rearrangements (balanced translocations, inversions) will not be detectable.
3. Single gene mutations usually determinable by gene sequencing will not be detectable.

CPT codes:
SNP MICROARRAY (6.0)
83890(1);83891(1);83892(3);83898(2);83894(3);83908(1);83896(335);83912(1)

SOTOS SYNDROMEGENE: NSD1 (histone-lysine N-methyltransferase, H3 lysine-36 and H4 lysine-20 specific)
CHROMOSOMAL LOCATION: 5q35
MODE OF INHERITANCE: autosomal dominant

Sotos syndrome is an overgrowth condition characterized by typical facial features (long narrow face, prominent narrow jaw, frontal bossing, malar flushing), and developmental delay/mental retardation. Among individuals with classic Sotos syndrome, approximately 50% of individuals of Japanese ancestry and 10% of individuals of non-Japanese ancestry have a 5q35 microdeletion that encompasses NSD1. Our laboratory offers MLPA analysis of the NSD1 gene which is designed to detect whole-exon or whole-gene deletions. Among individuals with classic Sotos syndrome, approximately 30-90% of individuals of non-Japanese ancestry and 10-12% of individuals of Japanese ancestry have an NSD1 sequence mutation. Our laboratory offers sequencing of all coding exons (exons 2-23) of the NSD1 gene. These assays are performed concurrently, unless specifically requested to be performed in a sequential manner. Prenatal diagnosis is available when a mutation has been identified in a family.

CPT codes:
SOTOS SYNDROME (NSD1) (SEQUENCING)
83890(1);83891(74);83892(37);83894(2);83898(37);83904(74);83909(74);83912(1)

SOTOS SYNDROME (NSD1) (MLPA)
83890(1);83896(41);83898(1);83909(1);83912(1);83914(1)

SOTOS SYNDROME (NSD1) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

STICKLER SYNDROME TYPE I

GENE: COL2A1 (collagen α1(II) chain)
CHROMOSOMAL LOCATION: 12q13.11-q13.2
MODE OF INHERITANCE: autosomal dominant

Stickler syndrome is an autosomal dominant connective tissue disorder that includes ophthalmologic (myopia, cataract, and retinal detachment), craniofacial (Pierre Robin sequence: micrognathia, glossoptosis, cleft palate), midface hypoplasia)), audiologic (hearing loss), and joint abnormalities (early arthritis, mild spondlyepiphyseal dysplasia). Mutations in three genes, COL2A1, COL11A1, and COL11A2, have been associated with the Stickler syndrome, termed Stickler syndrome type I, II, and III respectively. Our laboratory offers DNA sequencing of all coding exons (exons 1-54) as well as MLPA analysis of select exons for the detection of whole-exon or whole-gene deletions or duplications within COL2A1. These analyses detect 80-90% of mutations in individuals with a clinical diagnosis of Stickler syndrome.
Prenatal testing is available when a mutation has been identified in a family.

Other diseases caused by mutations in COL2A1:
      Achondrogenesis Type II (OMIM# 200610)
      Kniest Dysplasia (OMIM# 156550)
      Spondyloepiphyseal Dysplasia, Congenita (OMIM# 183900)
      Spondyloepimetaphyseal Dysplasia Strudwick type (OMIM# 184250)
      Spondyloperipheral Dysplasia (OMIM# 271700)
      Early-onset arthropathy
      Avascular necrosis of the femoral head, primary (ANFH) (OMIM# 08805)
      Autosomal dominant rhegmatogenous retinal detachment (ARDD)

CPT codes:
STICKLER SYNDROME (COL2A1) (SEQUENCING)
83890(1);83891(108);83892(54);83894(3);83898(54);83904(108);83909(108);83912(1)

STICKLER SYNDROME (COL2A1) (MLPA)
83890(1);83896(30);83898(1);83909(1);83912(1);83914(1)

STICKLER SYNDROME (COL2A1) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

TAY-SACHS DISEASE

GENE: HEXA (beta-hexosaminidase alpha chain)
CHROMOSOMAL LOCATION: 15q23-q24
MUTATIONS ANALYZED: 1277insTATC, IVS12+1(G->C), IVS 7+1(G->A)/G269S, and 7.6kb del
CARRIER FREQUENCY: 1 in 30 (Ashkenazi Jewish or French Canadian); 1 in 256 (Other)
**Carrier frequency in Cajun and Old Order Amish populations may be higher
MODE OF INHERITANCE: autosomal recessive

Classic Tay-Sachs disease (TSD) is a progressive neurodegenerative condition with typical onset between 3-6 months of age. There are also juvenile and adult forms of TSD. In almost all cases of Tay-Sachs disease there is a mutation in the HEXA gene, which can be detected using a panel of 5 mutations. Specifically, 98% of mutations in the Ashkenazi Jewish population are detected by this screen; 80-85% of mutations in the French Canadian population; and 38% of mutations in individuals who are neither of Ashkenazi Jewish nor French Canadian ancestry. The American College of Obstetrics & Gynecology (ACOG) recommends carrier screening for couples in which at least one person is of Ashkenazi Jewish or French Canadian ancestry. Direct DNA analysis is also available for patients who have signs or symptoms suggestive of this disorder. Prenatal diagnosis is available when mutations in the family are known.

CPT codes:
TAY-SACHS DISEASE
83890(1);83891(1);83892(3);83894(4);83898(4);83912(1)

TUBEROUS SCLEROSIS

GENE: TSC1 (not permitted to test TSC2)
CHROMOSOMAL LOCATION: 9q34
MODE OF INHERITANCE: autosomal dominant

Tuberous sclerosis complex (TSC) involves abnormalities of the skin (hypomelanotic macules, facial angiofibromas, shagreen patches, fibrous facial plaques, ungual fibromas), brain (cortical tubers, subependymal nodules, seizures, mental retardation/developmental delay), kidney (angiomyolipomas, cysts), and heart (rhabdomyomas, arrhythmias). Two-thirds of individuals with TSC have a de-novo mutation. Our laboratory offers sequencing and MLPA of the entire coding region for TSC1.
Prenatal testing is available when a mutation has been identified in a family.

CPT codes:
TUBEROUS SCLEROSIS TYPE 1 (TSC1) (SEQUENCING)
83890(1);83891(1);83894(21);83898(21);83904(42);83909(42);83912(1)

TUBEROUS SCLEROSIS TYPE 1 (TSC1) (MLPA)
83890(1);83896(30);83898(1);83909(1);83914(1);83912(1)

TUBEROUS SCLEROSIS TYPE 1 (TSC1) (KNOWN MUTATION)
83890(1);83891(1);83894(1);83898(1);83904(2);83909(2);83912(1)

UNIPARENTAL DISOMY

Uniparental disomy (UPD) arises when an individual inherits two copies of a chromosome pair from one parent and no copy from the other parent. When this abnormality is inherited, it may lead to health concerns in a child. UPD can result in rare recessive disorders, or developmental problems due to the effects of imprinting. UPD may also occur with no apparent impact on the health and development of and individual. Our laboratory offers UPD testing for chromosomes 7, 14, and 15.

CPT codes:
UNIPARENTAL DISOMY (samples from mother, father, child required)
83890(1);83891(3);83909(18);83898(18);83912(1)

VON HIPPEL-LINDAU

GENE: VHL (von Hippel-Lindau tumor suppressor)
CHROMOSOMAL LOCATION: 3p25-26
INCIDENCE: 1 in 36,000
MODE OF INHERITANCE: autosomal dominant

von Hippel-Lindau syndrome (VHL syndrome) is characterized by hemangioblastomas of the brain, spinal cord, and retina; renal cysts and clear cell renal cell carcinoma; pheochromocytoma; and endolymphatic sac tumors. Early recognition of VHL syndrome may allow for timely intervention and improved outcome. Our laboratory offers DNA sequencing of the VHL gene for the identification of mutations in this gene as well as deletion analysis for the detection of full gene deletions. An estimated 97% of cases can be detected using a combination of these methods. Prenatal diagnosis is available when the VHL mutation has been identified in a family.

CPT codes:
VON HIPPEL-LINDAU DISEASE (VHL) (SEQUENCING AND MLPA)
83890(1);83891(1);83894(6);83898(4);83896(27);83904(12);83914(1);83909(1);83912(1)

VON HIPPEL-LINDAU DISEASE (VHL) (MLPA ONLY)
83890(1);83896(27);83898(1);83909(1);83914(1);83912(1)

VON HIPPEL-LINDAU DISEASE (VHL) (KNOWN MUTATION)
83890(1);83891(1);83894(2);83898(1);83904(2);83912(1)

WAARDENBURG SYNDROME (TYPE 1, 2A, 3, 4)

GENE: PAX3 (paired box gene 3) – WS1 and WS3
MITF (micropthalmia-associated transcription factor) – WS2A
SOX10 (sex determining region Y-box 10) – WS2A and WS4
EDNRB (endothelin receptor type B) – WS4
EDN3 (endothelin 3) – WS4
CHROMOSOMAL LOCATION: 2q35 (PAX3); 3p14 (MITF); 22q13 (SOX10); 13q22 (EDNRB); 20q13.2-q13(EDN3)
MODE OF INHERITANCE: autosomal dominant; autosomal recessive with EDNRB or EDN3 mutations

Waardenburg syndrome (WS) is typically characterized by hearing loss and pigmentary changes of the iris, hair, and skin. The clinical phenotypes of WS type 1 and WS type 2 often overlap. The W-index can be calculated to delineate the more likely diagnosis.
Our laboratory offers sequencing of the PAX3, MITF, SOX10, EDNRB, and EDN3 genes. Mutations in the PAX3 gene have been identified in greater than 90% of patients with the clinical diagnosis of WS1 (with lateral displacement of the inner canthi). Mutations in the PAX3 gene are also responsible for WS type 3 (with limb defects). Mutations in the MITF gene have been identified in 10-20% of patients with the clinical diagnosis of WS type 2 (W-index is typically <1.95).
Mutations in the SOX10 gene have been identified in patients with clinically diagnosed WS type 2 and WS type 4 (with Hirschsprung disease and W-index is typically <1.95). Mutations in the EDNRB and EDN3 genes have been identified in patients with clinically diagnosed WS type 4 (with Hirschsprung disease and W-index is typically <1.95). Mutations within the EDNRB and EDN3 genes have also been implicated in isolated Hirschsprung disease (congenital intestinal aganglionosis). Mutations within the EDNRB gene have also been implicated in ABCD syndrome, an autosomal recessive condition characterized by albinism, black lock at temporal occipital region, Hirschsprung disease, and deafness. Mutations within the EDN3 gene have also been described in patients with congenital central hypoventilation syndrome.
Prenatal diagnosis is available when a mutation(s) has been identified in the family.

CPT codes:
WAARDENBURG SYNDROME TYPE 1/TYPE 3 (PAX3) (SEQUENCING)
83890(1);83891(1);83894(18);83898(9);83904(18);83912(1)

WAARDENBURG SYNDROME TYPE 1/TYPE 3 (PAX3) (KNOWN MUTATION)
83890(1);83891(1);83894(2);83898(1);83904(2);83912(1)

WAARDENBURG SYNDROME TYPE 1/TYPE 3/TYPE 2 (PAX3/MITF) (MLPA)
83890(1);83896(36);83898(1);83914(1);83909(1);83912(1)

WAARDENBURG SYNDROME TYPE 2 (MITF) (SEQUENCING)
83890(1);83891(1);83894(8);83898(8);83904(16);83909(16);83912(1)

WAARDENBURG SYNDROME TYPE 2 (MITF) (KNOWN MUTATION)
83890(1);83891(1);83894(1);83898(1);83904(2);83909(2);83912(1)

WAARDENBURG SYNDROME TYPE 2 and TYPE 4 (SOX10) (SEQUENCING)
83890(1);83891(10);83892(5);83894(1);83898(5);83904(10);83909(10);83912(1)

WAARDENBURG SYNDROME TYPE 2 and TYPE 4 (SOX10) (MLPA)
83890(1);83896(35);83898(1);83909(1);83912(1);83914(1)

WAARDENBURG SYNDROME TYPE 2 and TYPE 4 (SOX10) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

WAARDENBURG SYNDROME TYPE 4 (EDN3) (SEQUENCING)
83890(1);83891(10);83894(1);83898(5);83892(5);83904(10);83909(10);83912(1)

WAARDENBURG SYNDROME TYPE 4 (EDN3) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

WAARDENBURG SYNDROME TYPE 4 (EDN3) (MLPA)
83890(1);83898(1);83896(41);83909(1);83914(1);83912(1)

WAARDENBURG SYNDROME TYPE 4 (EDNRB) (SEQUENCING)
83890(1);83891(18);83894(1);83898(9);83892(9);83904(18);83909(18);83912(1)

WAARDENBURG SYNDROME TYPE 4 (EDNRB) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

WILSON DISEASE

GENE: ATP7B (Copper-transporting ATPase 2)
CHROMOSOMAL LOCATION: 13q14.3-q21.1
MODE OF INHERITANCE: autosomal recessive

Wilson disease is a disorder of copper metabolism that can present with hepatic, neurologic, or psychiatric disturbances, or a combination of these. Copper accumulation in tissues and organs can lead to liver disease, neurological symptoms including movement disorders, dysarthria, dystonia, migraines and seizures; and psychiatric symptoms including depression, personality changes and psychoses. The age of onset can be from childhood to adulthood; signs and symptoms are rarely observed in children under 3 years of age. Children tend to present with liver disease as their primary symptom, whereas most neurological and psychiatric symptoms tend to arise in adulthood. Our laboratory offers DNA sequencing of all coding exons (exons 1-21) as well as MLPA analysis of select exons for the detection of whole-exon or whole-gene deletions or duplications within ATP7B. These analyses detect approximately 98% of mutations in patients with a clinical diagnosis of Wilson disease.
Prenatal testing is available when the mutations are known in the family.

CPT codes:
WILSON’S DISEASE (ATP7B) (SEQUENCING)
83890(1);83891(50);83892(25);83894(2);83898(25);83904(50);83909(50);83912(1)

WILSON’S DISEASE (ATP7B) (MLPA)
83890(1);83896(28);83898(1); 83909(1);83912(1);83914(1)

WILSON’S DISEASE (ATP7B) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

X-CHROMOSOME INACTIVATION STUDIES

In females, one of the two X chromosomes becomes randomly inactivated early in embryogenesis to allow for dosage compensation of X-linked genes. In any one female somatic cell, the inactive X chromosome may be either the paternal or maternal X chromosome. If a particular X chromosome is significantly inactivated more frequently than the other, the X inactivation pattern is skewed. If a female carries a disease-causing mutation on one of her X chromosomes, she normally would not show signs of the disease. However, skewed X inactivation may result in symptoms of an X-linked disease if the chromosome carrying the mutation is preferentially active. Skewed patterns of inactivation in female carriers of a number of X-linked disorders have been observed. X-chromosome inactivation studies are useful in diagnosing such disorders and determining carrier status of family members. X- chromosome inactivation studies may also be helpful in the determination of pathogenicity of an alteration of an X-linked gene (in the carrier mother).

By using the methylation-sensitive restriction enzyme HpaII and PCR amplification of a (CAG)n triplet repeat region in the androgen receptor gene on the X chromosome (Xq11-q12), the methylation status of both the maternal and paternal X chromosome is determined. This enzyme digests DNA on the active X chromosome, but does not cut sites on the inactive X chromosome. The quantitative PCR of androgen receptor repeats is compared with and without digestion to determine X inactivation ratio. A pattern of 50-69% is consistent with normal, random X inactivation. A mildly skewed inactivation pattern is 70-79% and a pattern of 80-100% is consistent with abnormal, skewed X inactivation.

CPT codes:
X CHROMOSOME INACTIVATION STUDY
83890(1);83891(1);83892(1);83898(2);83909(2);83912(1)

X-LINKED LYMPHOPROLIFERATIVE DISEASE (XLP)

GENE: SH2D1A (SH domain protein 1A)
CHROMOSOMAL LOCATION: Xq26

XLP disease is a genetic autoimmune disease in which the patient has an abnormally low number of cytotoxic killer T cells, and is particularly susceptible to the Epstein-Barr virus. Our laboratory offers DNA sequencing for the identification of mutations in the SH2D1A gene. Carrier testing is available for the mothers and sisters of boys with a known mutation. Prenatal diagnosis is available when the XLP mutation has been identified in a family.

CPT codes:
X-LINKED LYMPHOPROLIFERATIVE DISEASE (SH2D1A) (SEQUENCING)
83890(1);83894(8);83898(4);83904(8);83912(1)

X-LINKED LYMPHOPROLIFERATIVE DISEASE (SH2D1A) (MLPA)
83890(1);83896(19);83898(1);83914(1);83909(1);83912(1)

X-LINKED LYMPHOPROLIFERATIVE DISEASE (SH2D1A) (KNOWN MUTATION)
83890(1);83891(1);83894(2);83898(1);83904(2);83912(1)

X-LINKED MENTAL RETARDATION SYNDROMES

X-linked mental retardation (XLMR) has a prevalence of 2.6/1,000 in the general population, accounting for over 10% of all cases of mental retardation. It is estimated that 2/3 of X-linked mental retardation is non-syndromic. Mutations in multiple X-linked genes cause both syndromic and non-syndromic mental retardation.

Individuals with a diagnosis of mental retardation, especially those in whom Fragile X syndrome has been ruled out, are candidates for testing. After a specific mutation is identified in a family, carrier testing can be performed for appropriate at-risk females (X-inactivation studies are also recommended and are available) and presymptomatic males. With appropriate genetic counseling, prenatal testing can be performed for females with an identified mutation.

Testing may be ordered by gene or in tiers.

Tier 1
DLG3
FTSJ1
JARID1C/SMCX
PHF6 (Borjeson-Forssman-Lehmann syndrome)
ZNF41

Our laboratory performs DNA sequencing of the following genes:
DLG3 (exons 1-19), FTSJ1 (exons 2-12), JARID1C/SMCX (exons 1-26), PHF6 (exons 2-10), and ZNF41 (exons 2-5).

CPT codes:
TIER 1 (DLG3; FTSJ1; JARID1C; PHF6; ZNF41)
CPT codes for complete sequencing of all 5 genes:
83890(1);83891(1);83894(5);83898(73);83892(1);83904(146);83908(146);83912(1)

CPT codes for individual genes:
DLG3 SEQUENCING
83890(1);83891(38);83892(19);83894(1);83898(19); 83904(38);83909(38);83912(1)

DLG3 KNOWN MUTATION
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

FTSJ1 SEQUENCING
83890(1);83891(22);83892(11);83894(1);83898(11);83904(28);83909(28);83912(1)

FTSJ1 KNOWN MUTATION
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

JARID1C/SMCX SEQUENCING
83890(1);83891(56);83892(28);83894(3);83898(28);83904(56);83909(56);83912(1)

JARID1C/SMCX KNOWN MUTATION
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

PHF6 (BORJESON-FORSSMAN-LEHMANN) SEQUENCING
83890(1);83891(20);83892(10);83894(1);83898(10);83904(20);83909(20);83912(1)

PHF6 (BORJESON-FORSSMAN-LEHMANN) KNOWN MUTATION
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

ZNF41 SEQUENCING
83890(1);83891(10);83892(5);83894(1);83898(5);83904(10);83909(10);83912(1)

ZNF41 KNOWN MUTATION
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

Tier 2
GDI1
FACL4/LACS4/ACSL4
OPHN1
PQBP1 (Renpenning syndrome 1)
TM4SF2/TSPAN7

Our laboratory performs DNA sequencing for the following genes:
GDI1 (exons 2-11), FACL4 (exons 4-17), OPHN1 (exons 2-24), PQBP1 (exons 1-6), and TM4SF2 (exons 1-7).
Our laboratory performs MLPA analysis for the following genes:
GDI1(exons 1, 5), FACL4/LACS4/ACSL4 (promoter, exons 10, 15), OPHN1 (exons 1, 4, 12, 20), PQBP1 (exons 1, 4), and TM4SF2/TSPAN7 (exons 1, 5).

TIER 2 (GDI1; LACS4; OPHN1; PQBP1; TM4SF2)
CPT codes for complete sequencing analyses of all 5 genes:
83890(1);83891(1);83894(5);83898(60);83892(1);83904(120);83908(120);83912(1)

CPT codes for complete MLPA analysis of all 5 genes:
83900(2);83901(89);83909(2);83912(1)

CPT codes for individual genes:
GDI1 (ASPERGER SYNDROME) SEQUENCING
83890(1);83891(22);83892(11);83894(1);83898(11);83904(22);83909(22);83912(1)

GDI1 (ASPERGER SYNDROME) MLPA
83890(1);83896(46);83898(1);83914(1);83909(1);83912(1)

GDI1 (ASPERGER SYNDROME) KNOWN MUTATION
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

LACS4/FACL4/ACSL4 (FATTY ACID CoA LIGASE/LONG CHAIN Acyl-CoA SYNTHASE) SEQUENCING
83890(1);83891(28);83892(14);83894(2);83898(14);83904(28);83909(28);83912(1)

LACS4/FACL4/ACSL4 (FATTY ACID CoA LIGASE/LONG CHAIN Acyl-CoA SYNTHASE) MLPA
83890(1);83896(46);83898(1);83914(1);83909(1);83912(1)

LACS4/FACL4/ACSL4 (FATTY ACID CoA LIGASE/LONG CHAIN Acyl-CoA SYNTHASE) KNOWN MUTATION
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

OPHN1 (OLIGOPHRENIN) SEQUENCING
83890(1);83891(46);83892(23);83894(3);83898(23);83904(46);83909(46);83912(1)

OPHN1 (OLIGOPHRENIN) MLPA
83890(1);83896(43);83898(1);83914(1);83909(1);83912(1)

OPHN1 (OLIGOPHRENIN) KNOWN MUTATION
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

PQBP1 (RENPENNING SYNDROME) SEQUENCING
83890(1);83891(10);83892(5);83894(5);83898(5);838904(10);83909(10);83912(1)

PQBP1 (RENPENNING SYNDROME) MLPA
83890(1);83896(43);83898(1);83914(1);83909(1);83912(1)

PQBP1 (RENPENNING SYNDROME) KNOWN MUTATION
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

TM4SF2/TSPAN7 SEQUENCING
83890(1);83891(14);83892(7);83894(1);83898(7);83904(14);83909(14);83912(1)

TM4SF2/TSPAN7 MLPA
83890(1);83896(43);83898(1);83914(1);83909(1);83912(1)

TM4SF2/TSPAN7 KNOWN MUTATION
83890(1);83891(2);83892(1);83894(1);83898(1);83904

Tier 3
ATRX (Alpha-thalassemia Mental Retardation syndrome)
FGD1 (Aarksog-Scott syndrome)
MID1 (X-linked Opitz G/BBB syndrome)
PLP1 (Pelizaeus-Merzbacher Disease)
RSK2/RPS6KA3 (Coffin Lowry syndrome)
SLC6A8 (Creatine transporter deficiency)

Our laboratory performs DNA sequencing for the following genes:
ATRX (exons 1-35), FGD1 (exons 1-18), MID1 (exons 2-10), PLP1 (exons 1-7), RSK2 (exons 1-22), and SLC6A8 (exons 1-13).
Our laboratory performs MLPA analysis for the following genes:
FGD1 (exons 1-18), MID1 (exons 1-10), PLP1 (exons 1-7), PQBP1 (exons 1-6), RSK2 (exons 1-22), and SLC6A8 (1-13).

TIER 3 (FGD1; MID1; PLP1; RSK2; SLC6A8)
CPT codes for complete sequencing analyses of all 5 genes:
83890(1);83891(1);83894(11);83898(105);83892(1);83904(210);83908(210);83912(1)

CPT codes for complete MLPA analysis of 4 genes (FGD1; MID1; PLP1; RSK2; SLC6A8):
83900(5);83901(174);83909(5);83912(1)

CPT codes for individual genes:
ATRX (ALPHA-THALASSEMIA MENTAL RETARDATION SYNDROME) SEQUENCING
83890(1);83891(70);83892(35);83894(4);83898(35);83904(70);83909(70);83912(1)

ATRX (ALPHA-THALASSEMIA MENTAL RETARDATION SYNDROME) KNOWN MUTATION
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

FGD1 (AARSKOG-SCOTT) SEQUENCING
83890(1);83891(36);83894(1);83898(18);83892(18);83904(36);83909(36);83912(1)

FGD1 (AARSKOG-SCOTT) MLPA
83890(1);83896(30);83898(1);83914(1);83909(1);83912(1)

FGD1 (AARSKOG-SCOTT) KNOWN MUTATION
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

MID1 (X-LINKED OPITZ G/BBB SYNDROME) SEQUENCING
83890(1);83891(20);83892(10);83894(1);83898(10);83904(20);83909(20);83912(1)

MID1 (X-LINKED OPITZ G/BBB SYNDROME) MLPA
83890(1);83896(23);83898(1);83914(1);83909(1);83912(1)

MID1 (X-LINKED OPITZ G/BBB SYNDROME) KNOWN MUTATION
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

PLP1 (PELIZAEUS-MERZBACHER DISEASE) SEQUENCING
83890(1);83891(14);83892(7);83894(1);83898(7);83904(14);83909(14);83912(1)

PLP1 (PELIZAEUS-MERZBACHER DISEASE) MLPA
83890(1);83896(31);83898(1);83914(1);83909(1);83912(1)

PLP1 (PELIZAEUS-MERZBACHER DISEASE) KNOWN MUTATION
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

RSK2/RPS6KA3 (COFFIN LOWRY SYNDROME) SEQUENCING
83890(1);83891(44);83892(22);83894(3);83898(22);83904(44);83909(44);83912(1)

RSK2/RPS6KA3 (COFFIN LOWRY SYNDROME) MLPA
83890(1);83896(43);83898(1);83914(1);83909(1);83912(1)

RSK2/RPS6KA3 (COFFIN LOWRY SYNDROME) KNOWN MUTATION
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

SLC6A8 (CREATINE TRANSPORTER DEFICIENCY; X-LINKED CREATINE DEFICIENCY) SEQUENCING
83890(1);83891(26);83892(13);83894(2);83898(13);83904(26);83909(26);83912(1)

SLC6A8 (CREATINE TRANSPORTER DEFICIENCY; X-LINKED CREATINE DEFICIENCY) MLPA
83890(1);83896(47);83898(1);83914(1);83909(1);83912(1)

SLC6A8 (CREATINE TRANSPORTER DEFICIENCY; X-LINKED CREATINE DEFICIENCY) KNOWN MUTATION
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

Tier 4:
AGTR2
ARHGEF6
MED12
PAK3
SLC16A2

Our laboratory performs DNA sequencing for the following genes:
AGTR2 (exon 3), ARHGEF6 (exons 1-22), MED12 (exons 1-45), PAK3 (exons 5-18), and SLC16A2 (exons 1-6).
Our laboratory performs MLPA analysis for the following genes:
AGTR2 (exon 1), ARHGEF6 (exons 1, 4, 9, 18), and PAK3 (exons 5, 10, 17, 18).

TIER 4 (AGTR2; ARHGEF6; MED12; PAK3; SLC16A2)
CPT codes for complete sequencing analyses of all 5 genes:
83890(1);83891(186);83894(8);83898(93);83892(93);83904(186);83909(186);83912(1)

CPT codes for complete MLPA analysis of 3 genes (AGTR2; ARHGEF6; PAK3):
83900(1);83901(42);83909(1);83912(1)

CPT codes for individual genes:
CPT codes:
AGTR2 (SEQUENCING)
83890(1);83891(8);83894(1);83898(4);83892(4);83904(8);83909(8);83912(1)

AGTR2 (MLPA)
83890(1);83896(47);83898(1);83914(1);83909(1);83912(1)

AGTR2 (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

ARHGEF6 (SEQUENCING)
83890(1);83891(44);83894(2);83898(22);83892(22);83904(44);83909(44);83912(1)

ARHGEF6 (MLPA)
83890(1);83896(47);83898(1);83914(1);83909(1);83912(1)

ARHGEF6 (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

MED12 (SEQUENCING)
83890(1);83891(90);83894(3);83898(45);83892(45);83904(90);83909(90);83912(1)

MED12 (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

PAK3 (SEQUENCING)
83890(1);83891(28);83894(1);83898(14);83892(14);83904(28);83909(28);83912(1)

PAK3 (MLPA)
83890(1);83896(47);83898(1);83914(1);83909(1);83912(1)

PAK3 (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

SLC16A2 (SEQUENCING)
83890(1);83891(16);83894(1);83898(8);83892(8);83904(16);83909(16);83912(1)

SLC16A2 (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

X-LINKED MENTAL RETARDATION/EPILEPSY PANELS

Testing may be ordered by gene or in panels.

Panel 1
Angelman-like syndrome (X-linked Christianson type) (SLC9A6 sequencing)
PCDH19 sequencing (females only)
Rett syndrome (MECP2 analysis)
Rett syndrome – atypical (STK9 analysis)

CPT codes for complete sequencing analyses of all 4 genes:
83890(1);83891(100);83894(6);83898(50);83892(50);83904(100);83909(100);83912(1)

CPT codes for complete MLPA analysis of 2 genes (MECP2, STK9):
83900(1);83901(89);83909(2);83912(1)

CPT codes by individual genes:
SLC9A6 (SEQUENCING)
83890(1);83891(32);83894(1);83898(16);83892(16);83904(32);83909(32);83912(1)

SLC9A6 (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

EPILEPSY WITH MENTAL RETARDATION (PCDH19) (SEQUENCING)
83890(1);83891(14);83894(1);83898(7);83892(7);83904(14);83909(14);83912(1)

EPILEPSY WITH MENTAL RETARDATION (PCDH19) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

RETT SYNDROME (MECP2) (SEQUENCING AND MLPA)
83890(1);83891(1);83894(11);83898(10);83900(1);83901(27);83904(5);83909(1);83912(1)

RETT SYNDROME (MECP2) (MLPA ONLY)
83890(1);83896(27);83898(1);83914(1);83909(1);83912(1)

RETT SYNDROME (MECP2) (KNOWN MUTATION)
83890(1);83891(1);83894(2);83898(2);83904(2);83912(1)

RETT SYNDROME – ATYPICAL (STK9; CDKL5) (SEQUENCING)
83890(1);83891(44);83894(22);83898(66);83904(44);83909(44);83912(1)

RETT SYNDROME – ATYPICAL (STK9; CDKL5) (MLPA)
83890(1);83896(46);83898(1);83914(1);83909(1);83912(1)

RETT SYNDROME – ATYPICAL (STK9; CDKL5) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

Panel 2
ATP6AP2 sequencing
OPHN1 analysis
Creatine (transporter) deficiency (SLC6A8 analysis)
SYN1 sequencing

CPT codes for complete sequencing analyses of all 4 genes:
83890(1);83891(122);83894(7);83898(61);83892(61);83904(122);83909(122);83912(1)

CPT codes for complete MLPA analysis of 2 genes (OPHN1, SLC6A8):
83900(1);83901(88);83909(2);83912(1)

CPT codes by individual genes:
ATP6AP2 (EPILEPSY) (SEQUENCING)
83890(1);83891(20);83892(10);83894(1);83898(10);83904(20);83909(20);83912(1)

ATP6AP2 (EPILEPSY) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

OPHN1 (OLIGOPHRENIN) SEQUENCING
83890(1);83891(46);83892(23);83894(3);83898(23);83904(46);83909(46);83912(1)

OPHN1 (OLIGOPHRENIN) MLPA
83890(1);83896(43);83898(1);83914(1);83909(1);83912(1)

OPHN1 (OLIGOPHRENIN) KNOWN MUTATION
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

SLC6A8 (CREATINE TRANSPORTER DEFICIENCY; X-LINKED CREATINE DEFICIENCY) SEQUENCING
83890(1);83891(26);83892(13);83894(2);83898(13);83904(26);83909(26);83912(1)

SLC6A8 (CREATINE TRANSPORTER DEFICIENCY; X-LINKED CREATINE DEFICIENCY) MLPA
83890(1);83896(47);83898(1);83914(1);83909(1);83912(1)

SLC6A8 (CREATINE TRANSPORTER DEFICIENCY; X-LINKED CREATINE DEFICIENCY) KNOWN MUTATION
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

SYN1 (EPILEPSY) (SEQUENCING)
83890(1);83891(30);83892(15);83894(1);83898(15);83904(30);83909(30);83912(1)

SYN1 (EPILEPSY) (KNOWN MUTATION)
83890(1);83891(2);83892(1);83894(1);83898(1);83904(2);83909(2);83912(1)

Y-CHROMOSOME DETECTION (SRY)

GENE: SRY (sex-determining region of Y)
CHROMOSOMAL LOCATION: Yp

Direct DNA analysis of the SRY gene is available for the rapid determination of the genetic factor responsible for maleness. Potential indications include: rapid gender determination of a fetus when the mother is a carrier of an X-linked recessive condition, determining risk for gonadal dysgenesis, or clarifying a discrepancy between karyotype and ultrasound imaging results.

CPT codes:
Y CHROMOSOME DETECTION (SRY)
83890(1);83891(1);83894(1);83898(2);83912(1)

Y-CHROMOSOME MICRODELETIONS

Almost 30% of males with impaired spermatogenesis have a Yq microdeletion. Our laboratory tests for 8 different microdeletions of the Y-chromosome, any one of which could interfere with spermatogenesis or cause spermatogenic arrest. We test for the presence of one marker (Sy277) within the DAZ (Deleted in AZoospermia) gene, four markers (Sy127, Sy1227, Sy85, and Sy243) within the AZF (AZoospermia Factor) gene, plus SRY, Amelogenin Y (Sy276), and ZFY(Sy238). This assay should be performed in conjunction with routine chromosome studies for evaluation of male infertility.

CPT codes:
Y-CHROMOSOME DNA ASSAY FOR MICRODELETIONS (ANALYSIS OF 8 MARKERS FOR MALE INFERTILITY)
83890(1);83891(1);83894(8);83900(1);83901(14);83912(1)

ZYGOSITY

Approximately one in every sixty births results in the delivery of twins. Twins are either dizygotic (fraternal) or monozygotic (identical). Our laboratory offers zygosity testing by comparing a panel of genetic markers between the twins.

CPT codes:
ZYGOSITY TESTING TWINS ALONE
83890(1);83891(2);83900(2);83901(30);83909(2);83912(1)

ZYGOSITY TESTING TWINS WITH ONE OR BOTH PARENTS
83890(1);83891(4);83900(4);83901(56);83909(4);83912(1) if both parents
83890(1);83891(3);83900(3);83901(42);83909(3);83912(1) if one parent

Contact|Directory|Maps & Directions|BUMC
October 30, 2009

Primary teaching affiliate
of BU School of Medicine