title: Characterization ofPABPN1expansion mutations in a large cohort of Mexican patients with oculopharyngeal muscular dystrophy (OPMD).
abstract: Oculopharyngeal muscular dystrophy (OPMD) is an autosomal-dominant, adult-onset disorder defined by blepharoptosis, dysphagia, and proximal muscle weakness. OPMD arises from heterozygous expansions of a trinucleotide (GCN) tract situated at the 5' region of the polyadenylate RNA binding protein 1 (PABPN1) gene. The frequency of a particular (GCN) expansion in a given population of patients with OPMD is largely influenced by the occurrence of founder mutations. Analysis of large groups of patients with OPMD from different ethnic origins will help to estimate the relative contribution of each expanded allele to the disease. The purpose of this study was to characterize the type ofPABPN1expanded alleles in a large cohort of OPMD individuals from Mexico. Molecular analysis procedures included genomic DNA extraction from blood leukocytes in each patient followed by PCR amplification ofPABPN1exon 1, and direct nucleotide sequencing of PCR products. A total of 102 patients with OPMD were included in the study. ExpandedPABPN1gene alleles were demonstrated in all patients: 65% (66 out of 102) had a (GCN)15 expansion while the remaining 35% (36 out of 102) exhibited a (GCN)13 expansion. This is one of the largest series of molecularly confirmed patients with OPMD in a non-Caucasian population. Ethnic-specific differences in the prevalence of specificPABPN1expansions must be considered for genetic screening of patients with OPMD.
authors.affiliation: Department of Genetics-Research Unit, Institute of Ophthalmology "Conde de Valenciana", Mexico City, Mexico.
authors.forename: Marisa
authors.initials: M
authors.lastname: Cruz-Aguilar
authors.affiliation: Department of Oculoplastics, Institute of Ophthalmology "Conde de Valenciana", Mexico City, Mexico.
authors.forename: Caroline
authors.initials: C
authors.lastname: Guerrero-de Ferran
authors.affiliation: Department of Oculoplastics, Institute of Ophthalmology "Conde de Valenciana", Mexico City, Mexico.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Tovilla-Canales
authors.affiliation: Department of Oculoplastics, Institute of Ophthalmology "Conde de Valenciana", Mexico City, Mexico.
authors.forename: Angel
authors.initials: A
authors.lastname: Nava-Castañeda
authors.affiliation: Department of Genetics-Research Unit, Institute of Ophthalmology "Conde de Valenciana", Mexico City, Mexico.|Faculty of Medicine, Department of Biochemistry, UNAM, Mexico City, Mexico.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Zenteno
mesh_terms: D001483:Base Sequence; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008800:Mexico; D008875:Middle Aged; D039141:Muscular Dystrophy, Oculopharyngeal / Q000235:genetics*; D009154:Mutation; D039122:Poly(A)-Binding Protein I / Q000235:genetics*; D017422:Sequence Analysis, DNA; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
chemical_list: C576588:PABPN1 protein, human; D039122:Poly(A)-Binding Protein I
keywords: Eye Abnormalities; Eye Diseases, Hereditary