Oculopharyngeal muscular dystrophy.
Autosomal dominant oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disease with worldwide distribution. It usually presents in the fifth or sixth decades with progressive dysphagia, eyelid ptosis, and proximal limb weakness. Unique intranuclear filament inclusions in skeletal muscle fibers are its morphological hallmark. Surgical correction of the ptosis and cricopharyngeal myotomy are the only therapies available. Autosomal dominant OPMD is caused by short (GCG)8-13 riplet-repeat expansions in the polyadenylation binding protein 2 (PABP2) gene, which is localized in chromosome 14q11. Autosomal recessive OPMD is caused by a double dose of a (GCG)7 PABP2 allele. The GCG expansions cause lengthening of a predicted polyalanine tract in the protein. The expanded polyalanine domains may cause polyalanine nuclear toxicity by accumulating as nondegradable nuclear filaments.
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Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Campus Nôtre-Dame, Quebec, Canada.
Rouleau
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Bouchard
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Fardeau
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Tomé
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D001763:Blepharoptosis / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D003680:Deglutition Disorders / Q000235:genetics; D006580:Genetic Carrier Screening; D006801:Humans; D018908:Muscle Weakness / Q000235:genetics; D018482:Muscle, Skeletal / Q000473:pathology; D009136:Muscular Dystrophies / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D010455:Peptides / Q000235:genetics; D010641:Phenotype; D039102:Poly(A)-Binding Proteins; D016601:RNA-Binding Proteins / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D018911:Trinucleotide Repeats
D010455:Peptides; D039102:Poly(A)-Binding Proteins; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; C019529:polyalanine