A multi-laboratory collaboration has lead to the identification of genetic changes in the human AEBP1 gene, which encodes the Aortic Carboxypeptidase-like Protein (ACLP), that leads to defective collagen assembly and a variant of Ehlers Danlos Syndrome (EDS). This research was published in the American Journal of Human Genetics.
Researchers from the Layne laboratory, including students Rose Zhao, Kathleen Tumelty, and William Monis, along with researchers from the Mayo Clinic, King Faisal Hospital in Saudi Arabia, and at the Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health have identified families with AEBP1 genetic mutations resulting in a constellation of clinical findings including joint laxity, redundant and hyperextensible skin, poor wound healing with abnormal scarring, osteoporosis, and other features reminiscent of EDS. This study also showed that the ACLP enhances collagen polymerization and binds to several fibrillar collagens via its discoidin domain. These studies support the conclusion that biallelic pathogenic variants in AEBP1 are the cause of this autosomal recessive EDS subtype.
Blackburn PR, Xu Z, Tumelty KE, Zhao RW, Monis WJ, Harris KG, Gass JM, Cousin MA, Boczek NJ, Mitkov MV, Cappel MA, Francomano CA, Parisi JE, Klee EW, Faqeih E, Alkuraya FS, Layne MD, McDonnell NB, Atwal PS. Biallelic Alterations in AEBP1 Lead to Defective Collagen Assembly and Connective Tissue Structure Resulting in a Variant of Ehlers-Danlos Syndrome. Am J Human Genetics 2018, in press.