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Germline mutations in the von Hippel–Lindau disease tumor suppressor gene: Correlations with phenotype
Author(s) -
Chen Fan,
Kishida Takeshi,
Yao Masahiro,
Hustad Thomas,
Glavac Damjan,
Dean Michael,
Gnarra James R.,
Orcutt Mary Lou,
Duh Fuh Mei,
Glenn Gladys,
Green Jane,
Hsia Y. Edward,
Lamiell James,
Li Hua,
Wei Ming Hui,
Schmidt Laura,
Tory Kalman,
Kuzmin Igor,
Stackhouse Tom,
Latif Farida,
Linehan W. Marston,
Lerman Michael,
Zbar Berton
Publication year - 1995
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.1380050109
Subject(s) - von hippel–lindau disease , biology , pheochromocytoma , missense mutation , genetics , multiple endocrine neoplasia type 2 , germline mutation , nonsense mutation , exon , germline , cancer research , gene , mutation , phenotype , disease , pathology , medicine , endocrinology
Abstract Von Hippel‐Lindau disease (VHL) is an inherited neoplastic disease characterized by a predisposition to develop retinal angiomas, central nervous system hemangioblastomas, renal cell carcinomas, pancreatie cysts, and pheochromocytomas. The VHL gene was recently isolated by positional cloning. The cDNA encodes 852 nucleotides in 3 exons. The VHL gene is unrelated to any known gene families. We identified germline mutations in 85/114 (75%) of VHL families. Clinical heterogeneity is a well‐known feature of VHL. VHL families were classified into 2 types based on the presence or absence of pheochromocytoma. The types of mutations responsible for VHL without pheochromocytoma (VHL type 1) differed from those responsible for VHL with pheochromocytoma (VHL type 2). Fifty‐six % of the mutations responsible for VHL type l were microdeletions/insertions, nonsense mutations, or deletions; 96% of the mutations responsible for VHL type 2 were missense mutations. Specific mutations in codon 238 accounted for 43% of the mutations responsible for VHL type 2. The mutations identified in these families will be useful in presymptomatic diagnosis. The identification of mutations associated with phenotypes contributes to the understanding of fundamental genetic mechanisms of VHL disease. © 1995 Wiley‐Liss, Inc.