Connexion

GENATLAS PHENOTYPE

last update : 16-11-2010

Symbol	VHL
Location	3p25.3
Name	Von Hippel-Lindau disease, type 1
Corresponding gene	VHL
related resource	VonHippel-Lindau disease von Hippel-Lindau disease germline mutation database
Main clinical features	dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign neoplasms, most frequently retinal, cerebellar, and spinal hemangioblastoma, renal cell carcinoma, pheochromocytoma, and pancreatic tumors
Genetic determination	autosomal dominant
Function/system disorder	neoplasia
	multisystem/generalized
	kidney and urinary tract
Type	disease

Gene product

Name

pVHL, implicated in a variety of functions among which degradation of HIFalpha

Mechanism(s)

Gene mutation	Chromosome rearrangement	Effect	Comments

various types			deletion of one or more exons, deletion/insertion mutations resulting in truncated protein, nonsense, frameshift mutations, mutations in consensus splice site. mainly truncating mutations and deletions in type 1, missense mutations more frequent in type 2

Remark(s)

mutations are detected in nearly 100 percent of affected individuals, 80 percent inherited, 20 percent de novo, over 300 different germline mutations identified

apparently sporadic pheochromocytoma associated with a novel, relatively conservative germline Gly104Val VHL gene mutation, which is localized within exon 1 of the VHL gene corresponding to the beta -domain of the VHL protein ( PMID: 18584357))

Genotype/Phenotype correlations

for VHL type 1, without pheochromocytoma

for VHL type 2A, without RCC, with pheochromocytoma (PHE) and hemangioblastoma (HAB), associated with high levels of VEGF

for VHL type 2B, including PHE, HAB, RCC

for VHL type 2C, PHE only

complete deletions of VHL protein have the lowest prevalence of ocular disease and the most favorable visual outcome