Chang-En Yu, ^* Junko Oshima, ^* Ying-Hui Fu, ^* Ellen M. Wijsman, Fuki Hisama, Reid Alisch, Shellie Matthews, Jun Nakura, Tetsuro Miki, Samir Ouais, George M. Martin, John Mulligan, Gerard D. Schellenberg

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 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.

C.-E. Yu and S. Matthews, Geriatric Research Education and Clinical Center (182B), Veterans Affairs Puget Sound Health Care System, Seattle Division, 1660 South Columbian Way, Seattle, WA 98108, USA, and Department of Neurology, University of Washington, Seattle, WA 98195, USA.
J. Oshima, Geriatric Research Education and Clinical Center (182B), Veterans Affairs Puget Sound Health Care System, Seattle Division, 1660 South Columbian Way, Seattle, WA 98108, USA, and Department of Pathology, University of Washington, Seattle, WA 98195, USA.
Y.-H. Fu, R. Alisch, J. Mulligan, Darwin Molecular Corporation, 1631 220th Street, S.E., Bothell, WA 98021, USA.
E. M. Wijsman, Division of Medical Genetics, Department of Medicine, and Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
F. Hisama, Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
J. Nakura and T. Miki, Department of Geriatric Medicine, Osaka University Medical School, 2-2 Yamadaoka Suita, Osaka 565, Japan.
S. Ouais, Section of Endocrinology, Damascus City Hospital, Damascus, Syria.
G. M. Martin, Department of Pathology, University of Washington, Seattle, WA 98195, USA.
G. D. Schellenberg, Geriatric Research Education and Clinical Center (182B), Veterans Affairs Puget Sound Health Care System, Seattle Division, 1660 South Columbian Way, Seattle, WA 98108, USA, and the Departments of Medicine, Neurology, and Pharmacology, University of Washington, Seattle, WA 98195, USA.
^* These authors contributed equally to this work.
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