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

作者：Berton Zbar, Takeshi Kishida, Fan Chen, Laura S. Schmidt, Eamonn Richard Maher, Frances M. Richards, Paul A. Crossey, Andrew R. Webster, Nabeel Ahmed Affara, Malcolm Andrew Ferguson-Smith, Hiltrud B. Brauch, Damjan Glavač, Hartmut P.H. Neumann, Sam Tisherman, John Joseph Mulvihill, David J. Gross, Taro Shuin, Jean M. Whaley, Berndt Seizinger, Nickolai Kley, Sylviane Olschwang, Cécile Boisson, Stephane Richard, CJM Lips, William Marston Linehan, Michael I. Lerman · 发表于：Human Mutation · 年份：1996 · DOI：10.1002/(sici)1098-1004(1996)8:4<348::aid-humu8>3.0.co;2-3 · 被引用次数：505 · 研究领域：Genetic and Kidney Cyst Diseases、Cancer, Hypoxia, and Metabolism、Hedgehog Signaling Pathway Studies

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.