Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9

Science. 2001 Aug 3;293(5531):864-7. doi: 10.1126/science.1062125.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Blotting, Southern
  • Chromosome Mapping
  • Chromosomes, Human, Pair 3 / genetics
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Diseases in Twins / genetics
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Introns*
  • Linkage Disequilibrium
  • Lod Score
  • Male
  • Microsatellite Repeats*
  • Muscles / metabolism
  • Mutation
  • Myotonic Dystrophy / genetics*
  • Myotonic Dystrophy / metabolism
  • Phenotype
  • Polymerase Chain Reaction
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Twins, Monozygotic
  • Zinc Fingers* / genetics

Substances

  • CNBP protein, human
  • DNA-Binding Proteins
  • RNA, Messenger
  • RNA-Binding Proteins