Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9.
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.
Liquori
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CL
Institute of Human Genetics; MMC 206, 420 Delaware Street SE, University of Minnesota, Minneapolis, MN 55455, USA.
Ricker
K
K
Moseley
M L
ML
Jacobsen
J F
JF
Kress
W
W
Naylor
S L
SL
Day
J W
JW
Ranum
L P
LP
D000483:Alleles; D015139:Blotting, Southern; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004200:Diseases in Twins / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns; D015810:Linkage Disequilibrium; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D009132:Muscles / Q000378:metabolism; D009154:Mutation; D009223:Myotonic Dystrophy / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014430:Twins, Monozygotic; D016335:Zinc Fingers / Q000235:genetics
C433227:CNBP protein, human; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins