Improved Detection of Germline Mutations in the Von-Hippel-Lindau-Disease Tumor Suppressor Gene

Author:

Stolle, C.

Glenn, G.

Zbar, B.

Humphrey, J. S.

Choyke, P.

Walther, M.

Pack, S.

Hurley, K.

Andrey, C.

Klausner, R.

Linehan, W. M.
Author Address

Zbar B NCI IMMUNOBIOL LAB FREDERICK CANC RES & DEV CTR BLDG 560 ROOM 12-89 FREDERICK CANC RES FACIL FREDERICK, MD 21702 USA NCI IMMUNOBIOL LAB FREDERICK CANC RES & DEV CTR FREDERICK, MD 21702 USA UNIV PENN GENET DIAGNOST LAB PHILADELPHIA, PA USA NCI GENET EPIDEMIOL BRANCH BETHESDA, MD 20892 USA NICHHD CELL BIOL & METAB BRANCH BETHESDA, MD USA NIH BETHESDA, MD 20892 USA NCI UROL ONCOL BRANCH BETHESDA, MD 20892 USA NCI PATHOL LAB BETHESDA, MD 20892 USA NCI OFF DIRECTOR BETHESDA, MD 20892 USA

Abstract:

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 de scribed in this article, it is now possible to identify germline mutations in virtually all families with VHL. Hum Mutat 12:417-423, 1998. (C) 1998 Wiley-Liss, Inc. [References: 23]

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