Characterization of VHL promoter variants in patients suspected of Von Hippel-Lindau disease

Eur J Med Genet. 2019 Mar;62(3):177-181. doi: 10.1016/j.ejmg.2018.07.006. Epub 2018 Jul 10.


Von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome in which carriers are at an increased risk of developing a variety of tumors in multiple organ systems. A clinical diagnosis of VHL is determined by the presence of specific clinical manifestations while a molecular genetic diagnosis results from a pathogenic variant in the VHL gene. The majority of mutations occur in VHL coding exons and DNA analysis of these regions has a reported sensitivity of nearly 100%. However, rare variants in the VHL gene promoter may be detected in some cases of suspected VHL disease. We report two cases where VHL promoter variants were detected and describe the role of multi-step mRNA and protein analysis in the diagnostic evaluation of these cases.

Keywords: Promoter; Protein; VHL; mRNA.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree
  • Promoter Regions, Genetic
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics*
  • Von Hippel-Lindau Tumor Suppressor Protein / metabolism
  • von Hippel-Lindau Disease / genetics*
  • von Hippel-Lindau Disease / pathology


  • RNA, Messenger
  • Von Hippel-Lindau Tumor Suppressor Protein
  • VHL protein, human