Get access

Genotype–phenotype correlations in VHL exon deletions

Authors

  • Alisdair McNeill,

    1. Department of Medical and Molecular Genetics, Institute of Biomedical Research, University of Birmingham, Birmingham, UK
    2. West Midlands Regional Genetics Service, Birmingham Women's Hospital, Edgbaston, Birmingham, UK
    Search for more papers by this author
  • Eleanor Rattenberry,

    1. West Midlands Regional Genetics Service, Birmingham Women's Hospital, Edgbaston, Birmingham, UK
    Search for more papers by this author
  • Richard Barber,

    1. West Midlands Regional Genetics Service, Birmingham Women's Hospital, Edgbaston, Birmingham, UK
    Search for more papers by this author
  • Pip Killick,

    1. Department of Medical and Molecular Genetics, Institute of Biomedical Research, University of Birmingham, Birmingham, UK
    Search for more papers by this author
  • Fiona MacDonald,

    1. West Midlands Regional Genetics Service, Birmingham Women's Hospital, Edgbaston, Birmingham, UK
    Search for more papers by this author
  • Eamonn R. Maher

    Corresponding author
    1. Department of Medical and Molecular Genetics, Institute of Biomedical Research, University of Birmingham, Birmingham, UK
    2. West Midlands Regional Genetics Service, Birmingham Women's Hospital, Edgbaston, Birmingham, UK
    • Department of Medical and Molecular Genetics, Institute of Biomedical Research West, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
    Search for more papers by this author

  • How to cite this article: McNeill A, Rattenberry E, Barber R, Killick P, MacDonald F, Maher ER. 2009. Genotype–phenotype correlations in VHL exon deletions. Am J Med Genet Part A 149A:2147–2151.

Abstract

Von Hippel-Lindau (VHL) syndrome is a dominantly inherited familial cancer syndrome caused by mutations in the VHL gene. VHL syndrome displays marked variation in expression and analysis of genotype–phenotype correlations have led to the concept of four subtypes of VHL syndrome (Types 1, 2A–C). Type 2 subtypes of VHL syndrome are characterized by the presence of pheochromocytoma and the three Type 2 subtypes are associated with differing risks of hemangioblastoma and renal cell carcinoma (RCC). Type 2 VHL syndrome is usually associated with surface missense mutations. Type 1 VHL syndrome is most commonly caused by germline exon deletions and truncating mutations and is characterized by susceptibility to hemangioblastomas and RCC but not pheochromocytoma. Recently, it has been suggested that large VHL gene deletions involving C3orf10 (HSPC300) might be associated with a low risk of RCC. We have reviewed the molecular and clinical characteristics of 127 individuals with germline VHL gene deletions. Large VHL gene deletions associated with a contiguous loss of C3orf10 were associated with a significantly lower lifetime risk of RCC than deletions that did not involve C3orf10. The risks of hemangioblastomas were similar in both groups. These results add to the growing body of evidence suggesting that patients with VHL syndrome caused by large VHL deletions that include C3orf10 may be designated as having a specific subtype (Type 1B) of the disorder. © 2009 Wiley-Liss, Inc.

Get access to the full text of this article

Ancillary