The 1396del A mutation and a missense mutation or a rare polymorphism of the WRN gene detected in a French Werner family with a severe phenotype and a case of an unusual vulvar cancer. Mutations in brief no. 136. Online.

The Werner's syndrome (WS) is a rare recessive disease characterized by an early onset of geriatric disorders. The Werner's syndrome gene (WRN) recently cloned, encodes for an helicase and therefore plays a role in DNA metabolism and DNA repair. Here, we report the study of a French family with two affected members and numerous cancers. Using the protein truncation test and sequencing, we identified a homozygous mutation in the WRN gene. This mutation generates a frame shift leading to a very short 391 amino acids truncated protein without the helicase motif. A particularly severe phenotype of the affected patient was associated with an unusual vulvar cancer traditionaly observed in elderly patients and therefore likely to be related to the Werner's syndrome. An additional substitution of G for A at nucleotidic position 1392 was also described. We suggest that a relation between genotype and phenotype could exist in the studied family.