Werner syndrome (WS) is an autosomal recessive genetic disease characterized by many age-related features. The gene responsible for WS (WRN) has been isolated and contains a helicase domain, but its function is unknown. Six different mutations throughout the WRN gene have been reported in the Japanese population. We have studied whether patients with a specific mutation exhibit distinct phenotypes from others. Fourteen patients with different mutations showed almost the same signs and symptoms and, therefore, the C terminal part of the product appears to be crucial for its functions, although other parts may be important as well. Haplotype analyses using 13 microsatellites covering the 2.8-3.0 cM WRN region showed that two out of six different mutations had founder chromosomes. These two founder chromosomes may be evenly distributed throughout the western part of Japan, suggesting that these mutations go back to a time earlier than 1400 years ago.