1. Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan.
- Author
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Zbar B, Kishida T, Chen F, Schmidt L, Maher ER, Richards FM, Crossey PA, Webster AR, Affara NA, Ferguson-Smith MA, Brauch H, Glavac D, Neumann HP, Tisherman S, Mulvihill JJ, Gross DJ, Shuin T, Whaley J, Seizinger B, Kley N, Olschwang S, Boisson C, Richard S, Lips CH, and Lerman M
- Subjects
- Adrenal Gland Neoplasms genetics, Asian People genetics, Ethnicity genetics, Europe, Family, Genotype, Humans, Introns, Israel, Japan, Kidney Neoplasms genetics, North America, Phenotype, Pheochromocytoma genetics, Point Mutation, Sequence Deletion, Von Hippel-Lindau Tumor Suppressor Protein, White People genetics, Genes, Tumor Suppressor, Ligases, Mutation, Proteins genetics, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases, von Hippel-Lindau Disease genetics
- 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.
- Published
- 1996
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