DNA-based diagnosis of the von Hippel-Lindau syndrome

Am J Ophthalmol. 2000 Feb;129(2):258-60. doi: 10.1016/s0002-9394(99)00328-1.


Purpose: To evaluate the etiology of a unilateral hemangioblastoma noted in a male with a family history remarkable only for spine surgery in the proband's father.

Methods: Genomic DNA was isolated from peripheral blood of family members, and the three exons of the von Hippel-Lindau gene were examined for mutations by direct sequencing.

Results: A three base pair (bp) deletion in exon 1 of the VHL gene was found in the father and both sons. This in-frame deletion results in the loss of a phenylalanine residue from the von Hippel-Lindau protein product, at amino acid position 76.

Conclusion: Genetic screening has confirmed that von Hippel-Lindau syndrome is responsible for the hemangioblastoma in the proband. Magnetic resonance imaging scans performed as a consequence of these results indicated spinal tumors present in the father and tumors present in the cerebellum of the proband's sibling. As close, lifelong follow-up is warranted with this disease, this case demonstrates the value of DNA testing in patients with ocular findings consistent with von Hippel-Lindau disease in the absence of a recognized family history.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Cerebellar Neoplasms / diagnosis
  • Cerebellar Neoplasms / genetics
  • Cerebellar Neoplasms / surgery
  • Child
  • DNA / analysis*
  • DNA Primers / chemistry
  • Gene Deletion*
  • Genes, Tumor Suppressor / genetics*
  • Genetic Testing
  • Hemangioblastoma / diagnosis
  • Hemangioblastoma / genetics
  • Hemangioblastoma / surgery
  • Humans
  • Laser Coagulation
  • Ligases*
  • Male
  • Pedigree
  • Point Mutation*
  • Proteins / genetics*
  • Retinal Neoplasms / diagnosis
  • Retinal Neoplasms / genetics
  • Retinal Neoplasms / surgery
  • Spinal Cord Neoplasms / diagnosis
  • Spinal Cord Neoplasms / genetics
  • Spinal Cord Neoplasms / surgery
  • Tumor Suppressor Proteins*
  • Ubiquitin-Protein Ligases*
  • Von Hippel-Lindau Tumor Suppressor Protein
  • von Hippel-Lindau Disease / complications
  • von Hippel-Lindau Disease / diagnosis
  • von Hippel-Lindau Disease / genetics*


  • DNA Primers
  • Proteins
  • Tumor Suppressor Proteins
  • DNA
  • Ubiquitin-Protein Ligases
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Ligases
  • VHL protein, human