Publication Date:
1996-04-12
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, C E -- Oshima, J -- Fu, Y H -- Wijsman, E M -- Hisama, F -- Alisch, R -- Matthews, S -- Nakura, J -- Miki, T -- Ouais, S -- Martin, G M -- Mulligan, J -- Schellenberg, G D -- P01 AG01751/AG/NIA NIH HHS/ -- R01 AG12019/AG/NIA NIH HHS/ -- T32 AG00057/AG/NIA NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1996 Apr 12;272(5259):258-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle Division, WA 98108, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8602509" target="_blank"〉PubMed〈/a〉
Keywords:
Aging/genetics
;
Amino Acid Sequence
;
Base Sequence
;
Chromosome Mapping
;
Chromosomes, Human, Pair 8/*genetics
;
*Cloning, Molecular
;
Codon, Terminator
;
DNA/metabolism
;
DNA Helicases/chemistry/*genetics
;
DNA, Complementary/genetics
;
Disease Susceptibility
;
Exodeoxyribonucleases
;
Exons/genetics
;
Female
;
Frameshift Mutation
;
Heterozygote
;
Homozygote
;
Humans
;
Male
;
Molecular Sequence Data
;
*Mutation
;
Neoplasms/etiology/genetics
;
RecQ Helicases
;
Sequence Alignment
;
Werner Syndrome/*genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink