I.15 Neuromuscular Disorders with Founder Effects in French Canada: why, where and how they contribute to the NMD field

Abstract

The French settlers of North America during the French Regime (1604-1763) were few and sparse on a vast continent. Understanding the early pioneer period and the subsequent growth of their descendants is key to explain the higher regional prevalence of certain Neuromuscular Disorders (NMD) in Canada. We will review the genetic impact of the various population bottlenecks that shaped the French Canadian gene pool. We will present a history of the identification of NMD with Canadian regional founder effects to emphasize how these large cohorts played a role in gene identification. Using oculopharyngeal muscular dystrophy (OPMD) as a prototype of FC founder diseases, we will chart how large FC cohorts disproportionally continue to contribute to our knowledge of these conditions. Myotonic muscular dystrophy type 1 (DM1) and Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) will also be discussed to underline the value of large cohort characterizations for granular clinical phenotyping and natural history studies. Lastly, we will discuss the contribution of rare recessive mutations and dominant mutations with variable prevalence to the identification of novel mutations relying on the mixed European and First Nation backgrounds of the French Canadian population.