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Title: Germline mutation screening and predictive testing in families with von Hippel-Lindau disease

Abstract

von Hippel-Lindau (VHL) disease is an autosomal inheritable disease that predisposes gene carriers to develop tumors in the eyes, central nervous system, kidney, adrenal gland, pancreas and epididymis. VHL type 1 is without phenochromocytoma (P); VHL type 2 is with P. Screening for germline mutations and preclinical diagnosis in families with VHL disease has become feasible since the VHL gene was isolated. We applied Southern blotting and hybridization with g7cDNA to detect rearrangements, PCR-SSCP and sequencing to detect missense, nonsense and splice mutations, and primer-specified restriction map modification to detect a P-specific missense mutation. In 48 apparently unrelated VHL families mainly from Germany, we identified 20/48 (42%) VHL mutations: 7 (14.5%) rearrangements, 9/48 (19%) missense mutations affecting nt505, 1/48 (2%) splice site mutation, 2/48 (4%) other missense mutations, and 1/48 (2%) nonsense mutation. The predominance of the nt505 mutation in 9 German families with VHL type 2 suggests that this genotype expresses the VHL/P disease pattern. Predictive testing for VHL gene carriers in families with specific mutations identified 7 asymptomatic gene carriers. VHL manifestations have been confirmed by clinical examination in two individuals. Early molecular diagnosis may result in a successful management of VHL disease and prolong survival of VHLmore » patients.« less

Authors:
; ;  [1]
  1. Univ. of Munich (Germany); and others
Publication Date:
OSTI Identifier:
134172
Report Number(s):
CONF-941009-
Journal ID: AJHGAG; ISSN 0002-9297; TRN: 95:005313-0908
Resource Type:
Journal Article
Journal Name:
American Journal of Human Genetics
Additional Journal Information:
Journal Volume: 55; Journal Issue: Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; PATIENTS; HEREDITARY DISEASES; NEOPLASMS; GENOTYPE; GENES; GENE MUTATIONS; SPLICING; DNA SEQUENCING; SCREENING; DETECTION; DIAGNOSIS; THERAPY; FEDERAL REPUBLIC OF GERMANY; GENETICS; DNA HYBRIDIZATION; POLYMERASE CHAIN REACTION

Citation Formats

Brauch, H, Glavac, D, and Pausch, F. Germline mutation screening and predictive testing in families with von Hippel-Lindau disease. United States: N. p., 1994. Web.
Brauch, H, Glavac, D, & Pausch, F. Germline mutation screening and predictive testing in families with von Hippel-Lindau disease. United States.
Brauch, H, Glavac, D, and Pausch, F. 1994. "Germline mutation screening and predictive testing in families with von Hippel-Lindau disease". United States.
@article{osti_134172,
title = {Germline mutation screening and predictive testing in families with von Hippel-Lindau disease},
author = {Brauch, H and Glavac, D and Pausch, F},
abstractNote = {von Hippel-Lindau (VHL) disease is an autosomal inheritable disease that predisposes gene carriers to develop tumors in the eyes, central nervous system, kidney, adrenal gland, pancreas and epididymis. VHL type 1 is without phenochromocytoma (P); VHL type 2 is with P. Screening for germline mutations and preclinical diagnosis in families with VHL disease has become feasible since the VHL gene was isolated. We applied Southern blotting and hybridization with g7cDNA to detect rearrangements, PCR-SSCP and sequencing to detect missense, nonsense and splice mutations, and primer-specified restriction map modification to detect a P-specific missense mutation. In 48 apparently unrelated VHL families mainly from Germany, we identified 20/48 (42%) VHL mutations: 7 (14.5%) rearrangements, 9/48 (19%) missense mutations affecting nt505, 1/48 (2%) splice site mutation, 2/48 (4%) other missense mutations, and 1/48 (2%) nonsense mutation. The predominance of the nt505 mutation in 9 German families with VHL type 2 suggests that this genotype expresses the VHL/P disease pattern. Predictive testing for VHL gene carriers in families with specific mutations identified 7 asymptomatic gene carriers. VHL manifestations have been confirmed by clinical examination in two individuals. Early molecular diagnosis may result in a successful management of VHL disease and prolong survival of VHL patients.},
doi = {},
url = {https://www.osti.gov/biblio/134172}, journal = {American Journal of Human Genetics},
number = Suppl.3,
volume = 55,
place = {United States},
year = {Thu Sep 01 00:00:00 EDT 1994},
month = {Thu Sep 01 00:00:00 EDT 1994}
}