title: (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.
authors.affiliation: Departamento de Genética, Facultad de Medicina, Universidad de la República, Avda. Gral. Flores 2125, 11800 Montevideo, Uruguay.
authors.forename: M
authors.initials: M
authors.lastname: Rodríguez
authors.forename: C
authors.initials: C
authors.lastname: Camejo
authors.forename: B
authors.initials: B
authors.lastname: Bertoni
authors.forename: C
authors.initials: C
authors.lastname: Braida
authors.forename: M M
authors.initials: MM
authors.lastname: Rodríguez
authors.forename: B
authors.initials: B
authors.lastname: Brais
authors.forename: M
authors.initials: M
authors.lastname: Medici
authors.forename: L
authors.initials: L
authors.lastname: Roche
mesh_terms: D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D018703:Founder Effect; D005789:Genealogy and Heraldry; D005820:Genetic Testing; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D039141:Muscular Dystrophy, Oculopharyngeal / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D039103:Poly(A)-Binding Protein II / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D014583:Uruguay
chemical_list: D039103:Poly(A)-Binding Protein II