(GCG) 11 founder mutation in the PABPN1 gene of OPMD Uruguayan families

Abstract

The dominant oculo-pharyngeal muscular dystrophy mutation consists of an expanded (GCN) 12–17 in the coding region of the PolyA Binding Protein Nuclear 1 gene. A founder effect has been demonstrated in Canadian and Bukhara Jewish populations with relatively high prevalence of this disease. Since the oculo-pharyngeal muscular dystrophy prevalence was remarkably high in Southern Uruguay, a founder effect was hypothesized. To identify the ancestral haplotype we determined the (GCN) repeat number and the variants of four intragenic SNPs in Uruguayan OPMD families and a control sample. All families carrying the mutation (GCG) 11(GCA) 3(GCG) shared a common ancestral haplotype and the age of the mutation was estimated in 37–53 generations by a composite likelihood method. One family carrying the (GCG) 9(GCA) 3(GCG) allele had a different haplotype. The genealogical and molecular data suggested that the common ancestors were Canary Islands' settlers that arrived in Uruguay in the XIX century.