Genotype-phenotype correlations in von Hippel-Lindau disease (VHL)

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:134369

Zbar, B; Chen, F; Kishida, T ^[1]

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1. NCI-FCRDC, Frederick, MD (United States); and others

Clinical heterogeneity is a well-recognized feature of VHL. We correlated germ line mutations with disease manifestation in 85 U.S. and Canadian VHL families. We compared disease manifestations both with the type of mutation and with specific mutations. The types of germ line mutation found in VHL families with pheochromocytomas (VHL/pheo) differed from the types found in VHL families without pheo. In VHL/pheo families, 96% of mutations were missense; in contrast, in VHL families without pheos, large deletions, nonsense, frameshift and missense mutations were found. Specific missense mutations 505 T to C, 686 T to C and 712 C to T were associated with characteristic disease manifestations. In VHL families with the 505 T to C mutation, pheos were frequent, but renal cell carcinoma (RCC) and pancreatic cysts did not occur. In a VHL family with the 686 T to C mutation, RCC was common, but pheos were rare. In VHL families with the 712 C to T mutation, both RCC and pheos were common. VHL/pheo families were characterized by missense VHL germ line mutations in the VHL gene. Characteristic disease phenotypes were associated with certain specific VHL mutations. The results suggest that a full-length mutant VHL protein is required to produce pheos.

• OSTI ID: 134369
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CORRELATIONS
GENE MUTATIONS
GENES
GENOTYPE
HEREDITARY DISEASES
MUTATION FREQUENCY
NEOPLASMS
NUCLEOTIDES
PATIENTS
PHENOTYPE
PROTEINS
SIZE