title: 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.
abstract: 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.
authors: Laboratoire d'Oncologie moléculaire (INSERM CRI9402), Centre Jean Perrin, BP 392,63011 Clemont-Ferrand, France.
authors: V
authors: V
authors: Vidal
authors: J O
authors: JO
authors: Bay
authors: F
authors: F
authors: Champomier
authors: M
authors: M
authors: Grancho
authors: L
authors: L
authors: Beauville
authors: C
authors: C
authors: Glowaczower
authors: D
authors: D
authors: Lemery
authors: M
authors: M
authors: Ferrara
authors: Y J
authors: YJ
authors: Bignon
mesh_terms: D004265:DNA Helicases / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005090:Exodeoxyribonucleases; D005260:Female; D006801:Humans; D020125:Mutation, Missense / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D053484:RecQ Helicases; D014846:Vulvar Neoplasms / Q000235:genetics*; D014898:Werner Syndrome / Q000235:genetics*; D000071657:Werner Syndrome Helicase
chemical_list: D004273:DNA, Neoplasm; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase