VHL mosaicism can be detected by clinical next-generation sequencing and is not restricted to patients with a mild phenotype

Eur J Hum Genet. 2014 Sep;22(9):1149-52. doi: 10.1038/ejhg.2013.279. Epub 2013 Dec 4.


The identification of Von Hippel-Lindau (VHL) mosaic mutations by conventional Sanger sequencing requires a labour-intensive enrichment step, thus explaining that mosaicism occurrence is underestimated in patients. Nowadays, it is possible to detect mutation in cell sub-populations by next-generation sequencing (NGS). Here, we described a diagnosis strategy using NGS with high coverage in a series of eight patients who were negative for a VHL abnormality by Sanger sequencing and deletion search. In two patients, a mosaic mutation in VHL was detected by NGS. One patient with a 5.7% mutated allele frequency had a severe phenotype and an early disease onset. In conclusion, clinical NGS in an hospital molecular oncogenetics laboratory is an efficient tool to identify VHL mosaic mutation. Its use may improve patient monitoring and genetic counseling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Female
  • Gene Frequency
  • Genetic Testing / methods*
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Male
  • Middle Aged
  • Mosaicism*
  • Phenotype*
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics*
  • von Hippel-Lindau Disease / diagnosis
  • von Hippel-Lindau Disease / genetics*


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