1996•Human MutationRequires access
Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan
Berton Zbar, Takeshi Kishida, Fan Chen, Laura S. Schmidt, Eamonn R. Maher, Frances M. Richards, Paul A. Crossey, Andrew R. Webster, Nabeel A. Affara, M.A. Ferguson‐Smith, Hiltrud Brauch, Damjan Glavač, Hartmut P.H. Neumann, Sam Tisherman, John J. Mulvihill, David J. Gross, Taro Shuin, Jean M. Whaley, Berndt Seizinger, Nickolai Kley, Sylviane Olschwang, Cécile Boisson, Stephane Richard, CJM Lips, W. Marston Linehan, Michael I. Lerman
Open publisher page 504 citations
Abstract
Germline mutation analysis was performed in 469 VHL families from North America, Europe, and Japan. Germline mutations were identified in 300/469 (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, Arg161Stop, Arg167Gln, Arg167Trp, 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.