A Nonsense Mutation in VHL Gene Causing Von Hippel-lindau Syndrome in a Large Chinese Family

Abstract BackgroundVon Hippel-Lindau (VHL) syndrome is a multi-organ neoplastic disease characterized by highly vascular and cystic tumors in central nervous system (CNS), retina and visceral lesions, which is mainly caused by germline mutations in the VHL gene. MethodsHere, a large consanguineous four-generation family with variant phenotypes of VHL disease was recruited and molecular genetics tested via Sanger sequencing. ResultGenetic investigation detected a c.351G>A nonsense mutation in the VHL gene, that altered the reading frame downstream and created a premature TGA stop signal, resulting in severely truncated pVHL (p.Trp117Ter). This mutation is absent from public databases, and the functional prediction bioinformatic tools demonstrated that the residue is conserved and the variant is highly likely to be deleterious. ConclutionThe c.315G>A nonsense mutation in VHL gene is the causal mutation of this kindred that may lead to clear familial aggregation of VHL disease because of the dysfunction of truncated pVHL.