Clinical Domain Working Groups
Limb Girdle Muscular Dystrophy Variant Curation Expert PanelMembership
The goal of this panel is to resolve the diagnosis of limb girdle muscular dystrophy (LGMD) by establishing an algorithm to genetically define clinically affected individuals without a confirmed diagnosis. LGMDs are a group of genetically heterogenous disorders sharing a common phenotype of proximal limb girdle pattern muscle weakness and wasting. They are chronically progressive, with no FDA approved therapies, and cause significant lifetime morbidity. Advances in technologies targeting gene replacement have led to a number of candidate drugs in the pipeline creating a pressing need to genetically diagnose patients. Indeed, a phase I/II gene therapy trial has delivered β-sarcoglycan to three LGMDR4 patients. The advent of broad-based free genetic testing programs in the United States offered by the MDA, and the Jain Foundation have increased the diagnosis and prevalence of each LGMD subtype. However, this approach has also created a new diagnostic challenge for clinically affected patients: with approximately 55% of patients having variants of uncertain significance (VUS) in an LGMD gene, and 23% with no mutation identified despite genetic testing. This VCEP will classify variants in established LGMD genes using the American College of Medical Genetics (ACMG) Guidelines. Our genes of interest for initial specification have either a strong or definitive gene curation classification, they are as follows: SGCA, SGCB, SGCD, SGCG, CAPN3, DYSF, ANO5, FKRP.
Expert Panel Status
Expert Panel Membership
Membership spans many fields, including genetics, medical, academia, and industry.