Zbar B, Kishida T, Chen F, Schmidt L, Maher E R, Richards F M, Crossey P A, Webster A R, Affara N A, Ferguson-Smith M A, Brauch H, Glavac D, Neumann H P, Tisherman S, Mulvihill J J, Gross D J, Shuin T, Whaley J, Seizinger B, Kley N, Olschwang S, Boisson C, Richard S, Lips C H, Lerman M
Laboratory of Immunobiology, Biological Carcinogenesis and Development Program, SAIC Frederick, Maryland, USA.
Hum Mutat. 1996;8(4):348-57. doi: 10.1002/(SICI)1098-1004(1996)8:4<348::AID-HUMU8>3.0.CO;2-3.
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.
对来自北美、欧洲和日本的469个VHL家系进行了种系突变分析。在300/469（63%）个受测家系中鉴定出种系突变；检测到137种不同的基因内种系突变。大多数种系VHL突变（124/137）出现在1 - 2个家系中；少数出现在四个或更多家系中。常见的种系VHL突变有：Phe76缺失、Asn78Ser、Arg161Stop、Arg167Gln、Arg167Trp和Leu178Pro。在这个大型系列研究中，有可能比较不同人群中相同种系突变的影响。种系VHL突变在白种人和日本VHL家系中产生相似的癌症表型。鉴定出的种系VHL突变产生了三种不同的癌症表型：（1）无嗜铬细胞瘤的肾癌，（2）有嗜铬细胞瘤的肾癌，以及（3）单独的嗜铬细胞瘤。带有表型信息的VHL种系突变目录对于VHL的诊断和预后研究以及VHL基因型 - 表型相关性研究应该是有用的。
