Von Hippel-Lindau (VHL) disease: distinct phenotypes suggest more than one mutant allele at the VHL locus

Hum Genet. 1991 Jun;87(2):207-10. doi: 10.1007/BF00204184.


As part of an attempt to locate the von Hippel-Lindau locus (VHL) on chromosome 3, we evaluated 41 families with von Hippel-Lindau disease from the United States and Canada. One large family was identified whose disease phenotype was distinct from typical VHL. The most common disease manifestation was pheochromocytoma occurring in 57% (27/47) of affected family members. Few (4/47) affected family members had symptomatic spinal or cerebellar hemangioblastomas; no affected family member had renal cell carcinoma (0/47) or pancreatic cysts (0/24). Previously, genetic analysis demonstrated that the disease manifestations in this family were linked to RAF1 and D3S18, markers shown to be linked to typical VHL. These results suggest that there are mutant alleles at the VHL locus associated with distinct tissue specificities.

MeSH terms

  • Adrenal Gland Neoplasms / etiology
  • Alleles
  • Carcinoma, Renal Cell / etiology
  • Female
  • Genetic Linkage
  • Hemangioma / etiology
  • Hemangiosarcoma / etiology
  • Humans
  • Kidney Neoplasms
  • Lod Score
  • Male
  • Pancreatic Cyst / etiology
  • Phenotype
  • Pheochromocytoma / etiology
  • Retinal Diseases / etiology
  • von Hippel-Lindau Disease / complications
  • von Hippel-Lindau Disease / genetics*