Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Advances in genetics lead to the identification of a growing number of distinct recessive muscular dystrophies (MD) and their causal genes. These new discoveries allow better diagnosis and genetic counseling and open the way to a specific understanding of the underlining pathology essential for the development of new treatments. We have recruited two distinct cohorts of French-Canadian families affected by two new forms of MD. Mutations in an integrin were uncovered in a cohort of 20 individuals from 16 families affected by a novel congenital muscular dystrophy with hyperlaxity (CMDH). In parallel, we have identified a probable mutation in another integrin in families of Acadian ancestry affected by a new childhood onset limb girdle muscular dystrophy (LGMD). These MD are only the second and third to be found to be caused by mutations in an integrin since the discovery in 1998 of mutation in ITGA7 in a very rare form of congenital MD. Integrins form a large family of transmembrane proteins involved in numerous functions. Their function in muscle is still not fully understood. We propose to investigate how mutations in these two integrins cause these new forms of MD and explore in more general the roles of integrins in normal muscle development and function. The identification of two new genes causing congenital muscular dystrophies will allow a better diagnostic and genetic counseling for Canadian and other ethnic families affected by a muscular dystrophy.