Author/Editor		Chen, Fan; Kishida, Takeshi; Yao, Masahiro; Hustad, Thomas; Glavač, Damjan; Dean, Michael; Gnarra, James R; Orcutt, Mary L; Duh, Fuh M; Glenn, Gladys
Title		Germline mutations in the von Hippel-Lindau disease tumor suppressor gene: correlations with phenotype
Type		članek
Source		Hum Mutat
Vol. and No.		Letnik 5, št. 1
Publication year		1995
Volume		str. 66-75
Language		eng
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, pancreatic 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 percent) 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 percent of the mutations responsible for VHL type 1 were microdeletions/insertions, nonsense mutations, or deletions; 96 percent of the mutations responsible for VHL type 2 were missense mutations. Specific mutations in codon 238 accounted for 43 percent 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.
Descriptors		GENES, SUPPRESSOR, TUMOR GERM-LINE MUTATION HIPPEL-LINDAU DISEASE ADRENAL GLAND NEOPLASMS BASE SEQUENCE DNA DNA MUTATIONAL ANALYSIS DNA PRIMERS GENOTYPE MOLECULAR SEQUENCE DATA PHENOTYPE PHEOCHROMOCYTOMA POINT MUTATION POLYMERASE CHAIN REACTION POLYMORPHISM (GENETICS)