Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan

✍ Scribed by Berton Zbar; Takeshi Kishida; Fan Chen; Laura Schmidt; Eamonn R. Maher; Frances M. Richards; Paul A. Crossey; Andrew R. Webster; Nabeel A. Affara; Malcolm A. Ferguson-Smith; Hiltrud Brauch; Damjan Glavac; Hartmut P.H. Neumann; Sam Tisherman; John J. Mulvihill; David J. Gross; Taro Shuin; Jean Whaley; Berndt Seizinger; Nickolai Kley; Sylviane Olschwang; Cecile Boisson; Stephane Richard; C.H.M. Lips; W. Marston Linehan; Michael Lerman

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 917 KB
• Volume: 8
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/(sici)1098-1004(1996)8:4<348::aid-humu8>3.0.co;2-3

✦ Synopsis

Germline mutation analysis was performed in 469 VHL families from North America, Europe, and Japan. Germline mutations were identified in 3001469 (63%) of the families tested; 137 distinct intragenic germline mutations were detected. Most of the germline VHL mutations (124/137) occurred in 1-2 families; a few occured in four or more families. The common germline VHL mutations were: delPhe76, Asn78Ser, Argl61Stop, Arg167Gln, Argl67Trp, and Leu178Pro. In this large series, it was possible to compare the effects of identical germline mutations in different populations. Germline VHL mutations produced similar cancer phenotypes in Caucasian and Japanese VHL families. Germline VHL mutations were identified that produced three distinct cancer phenotypes: ( 1) renal carcinoma without pheochromocytoma, (2) renal carcinoma with pheochromocytoma, and (3) pheochromocytoma alone.

The catalog of VHL germline mutations with phenotype information should be useful for diagnostic and prognostic studies of VHL and for studies of genotype-phenotype correlations in VHL.