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Triplet repeat expansion in neuromuscular disease
Author(s) -
Lieberman Andrew P.,
Fischbeck Kenneth H.
Publication year - 2000
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/(sici)1097-4598(200006)23:6<843::aid-mus2>3.0.co;2-8
Subject(s) - neuromuscular disease , medicine , physical medicine and rehabilitation , neuroscience , disease , psychology
Expansions of unstable trinucleotide repeats cause at least 15 inherited neurologic diseases. Here we review what has been learned of three neuromuscular diseases caused by this type of mutation. X‐linked spinal and bulbar muscular atrophy is a motor neuronopathy caused by a CAG repeat expansion in the androgen receptor gene. The mutated protein has an expanded polyglutamine tract, forms intranuclear aggregates, and mediates neurodegeneration through a toxic gain‐of‐function mechanism. Oculopharyngeal muscular dystrophy is a dominantly inherited myopathy caused by a GCG/polyalanine expansion in the gene encoding poly(A)‐binding protein 2. Myotonic dystrophy is a clinically variable multisystem disease caused by a CTG expansion in the 3′ untranslated region of the myotonin gene. For each of these disorders, we summarize the clinical and pathologic features and review current understanding of the molecular mechanisms underlying their pathogenesis. © 2000 John Wiley & Sons, Inc. Muscle Nerve 23: 843–850, 2000