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H. Mejia–Lopez, E. Pompa–Mera, A. Nava–Castañeda, L. Garnica–Hayashi, J. Zenteno; GCG Triplet Expansions in the PABP–2 Gene in Mexican Families With Autosomal Dominant Oculopharyngeal Muscular Dystrophy . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1839.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Oculopharyngeal muscular dystrophy (OFMD) is an autosomal dominant, late–onset disease mainly characterized by dysphagia, progressive ptosis of the eyelids, and distal limb muscle weakness. The condition is caused by short amplifications of a GCG triplet in the gene encoding the poly(A)–binding protein–2 (PABP–2), located on chromosome 14q11. The severity of the clinical picture as well as the number of repeats that cause the disease is variable ranging between (GCG)8–13, (GCG)6 being the usual triplet number found in unaffected individuals. The allele (GCG)9 has been demonstrated to be the most prevalent allele in different series of affected families. We describe the molecular analyses of the PABP–2 gene in three probands from three unrelated Mexican families with OFMD Methods: Proband 1 initiated symptoms at the age of 45 when bilateral progressive ptosis was noted, followed by dysphagia at the age of 50. Moderate distal limb muscle weakness was also observed; she had at least four alive affected relatives; proband 2 first noticed bilateral ptosis at the age of 61 years, followed by dysphagia since the age of 65; proband 3 initiated symptoms at the age of 48 when he noticed progressive dysphagia followed 2 years after by bilateral progressive ptosis; After informed consent DNA was obtained from peripheral blood leukocytes in each proband; a fragment of the PABP–2 gene containing the GCG tract was PCR amplified and the products of amplification were cloned in plasmid vectors using a TA cloning strategy. Results: Individual clones from each patient were fluorescently sequenced allowing the characterization of both alleles in each subject. In all three subjects the expanded allele corresponded to (GCG)11 with the normal allele being (GCG)6. Conclusions: No genotype–phenotype correlation was evident in these three probands with OFMD caused by identical (GCG)11 triplet expansion. The (GCG)11 allele have been shown to be an uncommon allele in previous series of affected individuals; this is the first study of the GCG expansion in the PABP–2 gene in Mexican patients with OFMD and the preliminary data suggest that (GCG)11 is a common allele in affected subjects in this population.
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