Walsh & Hoyt: Clinical and Molecular Genetics

VHLD is an autosomal-dominant disorder transmitted with incomplete penetrance. It results from a defect in a tumor-suppressor gene, a complex gene of approximately 50 kb located on chromosome 3p25.5. The von Hippel-Lindau gene consists of three exons and encodes a 30-kDa protein consisting of 213 amino acid residues. VHLD-associated neoplasms are hypervascular and overproduce angiogenic peptides such as vascular endothelial growth factor (VEGF). It is postulated that ability of pVHL30 to suppress tumor formation is linked to its ability to negatively regulate hypoxia-inducible proteins.