Abstract
Myotonic dystrophy (DM), the most common form of muscular dystrophy in adults, can be caused by a mutation on either chromosome 19q13 (DM1) or 3q21 (DM2/PROMM). DM1 is caused by a CTG expansion in the 3' untranslated region of the dystrophia myotonica-protein kinase gene (DMPK). Several mechanisms have been invoked to explain how this mutation, which does not alter the protein-coding portion of a gene, causes the specific constellation of clinical features characteristic of DM. We now report that DM2 is caused by a CCTG expansion (mean approximately 5000 repeats) located in intron 1 of the zinc finger protein 9 (ZNF9) gene. Parallels between these mutations indicate that microsatellite expansions in RNA can be pathogenic and cause the multisystemic features of DM1 and DM2.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alleles
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Blotting, Southern
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Chromosome Mapping
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Chromosomes, Human, Pair 3 / genetics
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Diseases in Twins / genetics
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Female
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Humans
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In Situ Hybridization, Fluorescence
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Introns*
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Linkage Disequilibrium
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Lod Score
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Male
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Microsatellite Repeats*
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Muscles / metabolism
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Mutation
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Myotonic Dystrophy / genetics*
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Myotonic Dystrophy / metabolism
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Phenotype
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Polymerase Chain Reaction
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA-Binding Proteins / chemistry
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RNA-Binding Proteins / genetics*
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RNA-Binding Proteins / metabolism
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Twins, Monozygotic
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Zinc Fingers* / genetics
Substances
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CNBP protein, human
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DNA-Binding Proteins
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RNA, Messenger
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RNA-Binding Proteins