The von Hippel-Lindau disease is an autosomal dominant genetic syndrome characterized by the development of multiple tumors, including hemangioblastoma of the central nervous system and retina, renal cyst or carcinoma, and pheochromocytoma. Pheochromocytomas are frequently bilateral in VHL patients and are observed in 10 to 19% of cases. The von Hippel-Lindau susceptibility gene (VHL) is located on the short arm of chromosome 3 (3p25–26). Mutations of VHL are found in most affected kindred. Loss of heterozygosity at the VHL locus affecting selectively the wild-type VHL allele is associated with tumor formation, as commonly observed with tumor suppressor genes. Interestingly, in most cases of sporadic renal carcinoma or hemangioblastoma, the VHL gene is also altered by mutation or hypermethylation. Furthermore, transfection of the wild-type VHL cDNA into renal carcinoma cells inhibits tumor development, whereas transfection of the mutant does not.
Cloning of the human VHL gene was first reported in 1993.