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

Abstract

Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset autosomal dominant myopathy found world-wide, but with the highest incidence in French-Canadians. Short GCG expansions in the poly(A) binding protein 2 (PABP2) gene were identified recently as the molecular basis for OPMD in French-Canadians. All French-Canadian cases of OPMD have been traced to a single founder couple [Bouchard, 1997: Neuromuscul Disord 7(Suppl):S5-S11]. Cultural links between French-Canadians and Cajuns suggest that this same founder couple may have transmitted the OPMD mutation to Cajuns as well. To determine if OPMD patients from Louisiana share a founder effect with French-Canadian families, we collected blood samples and muscle biopsies from several Cajuns with OPMD for mutation and linkage studies. We found a unique 'GCA GCG GCG' insertion mutation in Cajuns. Consistent with these sequence data, we identified a disease haplotype in our Cajun families that is different from the ancestral haplotype defined in French-Canadians. These data prove that different founders introduced the PABP2 mutation to Cajuns and French-Canadians and lend support to emerging genealogical data suggesting that French-Canadians and Cajuns represent distinct immigrant groups from France.