Project Abstract

Susan E. Sparks, MD, PhD is a board certified Pediatrician, Clinical Geneticist, and Clinical Biochemical Geneticist who has experience in muscular dystrophy and clinical research in defects of glycosylation. Her main career goal, both short and long term is to combine clinical practice and patient care with translational research. She will become the expert in glycosylation defects of muscular dystrophy at the CNMC Wellstone MDCRC. This expertise will contribute to the overall goals of the CNMC Wellstone Center of the diagnosis and treatment of muscular dystrophies. She is committed to becoming an excellent Physician Scientist with independent research funding. In this proposal, Dr. Sparks intends to test the following hypothesis: The neurologic and muscle phenotype of the congenital muscular dystrophies (CMD) are caused by defects in enzymes that glycosylate alpha-dystroglycan and other components of the muscle fiber. To this end she will work with the mentor and mentor's resources at the CNMC Wellstone MDCRC to ascertain and characterize patients with congenital muscular dystrophies that have a defect in glycosylation.

Patients with CMD will be identified that have abnormal glycosylation of ?-dystroglycan. They will then be evaluated for mutations in the 6 glycosylation genes known to cause CMD. Those without identifiable defects will be characterized biochemically. Enzyme analysis and evaluation of the transport and activation of sugars will be performed in close collaboration with Drs. Gahl and Krasnewich at the National Institutes of Health. These muscular dystrophy cases with abnormal glycosylation provide an opportunity to elucidate the metabolic bases of muscular dystrophy. It is expected that the proposed research will lead to a better understanding of the biochemical steps involved in glycosylation of ?-dystroglycan. It is also expected that one or more novel genes/proteins involved in this glycosylation process will be identified.