Positional cloning of the Werner's syndrome gene

Science. 1996 Apr 12;272(5259):258-62. doi: 10.1126/science.272.5259.258.


Werner's syndrome (WS) is an inherited disease with clinical symptoms resembling premature aging. Early susceptibility to a number of major age-related diseases is a key feature of this disorder. The gene responsible for WS (known as WRN) was identified by positional cloning. The predicted protein is 1432 amino acids in length and shows significant similarity to DNA helicases. Four mutations in WS patients were identified. Two of the mutations are splice-junction mutations, with the predicted result being the exclusion of exons from the final messenger RNA. One of the these mutations, which results in a frameshift and a predicted truncated protein, was found in the homozygous state in 60 percent of Japanese WS patients examined. The other two mutations are nonsense mutations. The identification of a mutated putative helicase as the gene product of the WS gene suggests that defective DNA metabolism is involved in the complex process of aging in WS patients.

Publication types

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

MeSH terms

  • Aging / genetics
  • Amino Acid Sequence
  • Base Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 8 / genetics*
  • Cloning, Molecular*
  • Codon, Terminator
  • DNA / metabolism
  • DNA Helicases / chemistry
  • DNA Helicases / genetics*
  • DNA, Complementary / genetics
  • Disease Susceptibility
  • Exodeoxyribonucleases
  • Exons / genetics
  • Female
  • Frameshift Mutation
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Neoplasms / etiology
  • Neoplasms / genetics
  • RecQ Helicases
  • Sequence Alignment
  • Werner Syndrome / genetics*
  • Werner Syndrome Helicase


  • Codon, Terminator
  • DNA, Complementary
  • DNA
  • Exodeoxyribonucleases
  • DNA Helicases
  • RecQ Helicases
  • WRN protein, human
  • Werner Syndrome Helicase

Associated data

  • GENBANK/L76937