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Improved detection of germline mutations in the von Hippel‐Lindau disease tumor suppressor gene
Author(s) -
Stolle Catherine,
Glenn Gladys,
Zbar Berton,
Humphrey Jeffrey S.,
Choyke Peter,
Walther McClellan,
Pack Svetlanna,
Hurley Kathy,
Andrey Carolyn,
Klausner Richard,
Linehan W. Marston
Publication year - 1998
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/(sici)1098-1004(1998)12:6<417::aid-humu8>3.0.co;2-k
Subject(s) - biology , germline , germline mutation , von hippel–lindau disease , genetics , tumor suppressor gene , gene , southern blot , mutation , cancer research , carcinogenesis , disease , pathology , medicine
von Hippel‐Lindau disease (VHL) is an inherited neoplastic disorder characterized by the development of tumors in the eyes, brain, spinal cord, inner ear, adrenal gland, pancreas, kidney, and epididymis. The VHL tumor suppressor gene was identified in 1993. Initial studies reported the detection of germline mutations in the VHL gene in 39–75% of VHL families. We used tests that detect different types of mutations to improve the frequency of detection of germline mutations in VHL families. The methods included quantitative Southern blotting to detect deletions of the entire VHL gene, Southern blotting to detect gene rearrangements, fluorescence in situ hybridization (FISH) to confirm deletions, and complete sequencing of the gene. Here we report that we have detected germline mutations in the VHL gene in 100% (93/93) of VHL families tested. In addition, we describe 13 novel intragenic VHL germline mutations. With the methodology described in this article, it is now possible to identify germline mutations in virtually all families with VHL. Hum Mutat 12:417–423, 1998. © 1998 Wiley‐Liss, Inc.