Unique PABP2 mutations in "Cajuns" suggest multiple founders of oculopharyngeal muscular dystrophy in populations with French ancestry

Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset autosomal domin ant myopathy found world-wide, but with the highest incidence in French-Can adians. Short GCG expansions in the poly(A) binding protein 2 (PABP2) gene were identified recently as the molecular basis for OPMD in French-Canadian s. All French-Canadian cases of OPMD have been traced to a single founder c ouple [Bouchard, 1997: Neuromuscul Disord 7(Suppl):S5-S11]. Cultural links between French-Canadians and Cajuns suggest that this same founder couple m ay have transmitted the OPMD mutation to Cajuns as well, To determine if OP MD patients from Louisiana share a founder effect with French-Canadian fami lies, we collected blood samples and muscle biopsies from several Cajuns wi th OPMD for mutation and linkage studies. We found a unique 'GCA GCG GCG' i nsertion mutation in Cajuns, Consistent with these sequence data, we identi fied a disease haplotype in our Cajun families that is different from the a ncestral haplotype defined in French-Canadians. These data prove that diffe rent founders introduced the PABP2 mutation to Cajuns and French-Canadians and lend support to emerging genealogical data suggesting that French-Canad ians and Cajuns represent distinct immigrant groups from France. Am. (C) 19 99 Wiley-Liss, Inc.