A nonsense mutation in causing Von Hippel-Lindau syndrome in a large Chinese family-a genetic study of familial neoplastic disease.

Von Hippel-Lindau (VHL) syndrome is a multi-organ neoplastic disease characterized by highly vascular and cystic tumors in the central nervous system (CNS), retina, and visceral lesions, which are mainly caused by germline mutations in . We aimed to detect novel mutations in gene in families with VHL. Here, a large consanguineous four-generation family with variant phenotypes of VHL syndrome was recruited, and its molecular genetics were tested Sanger sequencing. And various tools and databases were used to predict the variant pathogenicity, frequency, and protein function. Genetic investigation detected a c.351G > A nonsense mutation in that altered the downstream reading frame and created a premature TGA stop signal, resulting in severely truncated pVHL (p.Trp117Ter). This mutation is absent from most public databases, and functional prediction bioinformatic tools demonstrated that this residue is conserved and that this variant is highly likely to be deleterious. The c.315G > A nonsense mutation in is the causal mutation of this kindred that may lead to clear familial aggregation of VHL syndrome because of the dysfunction of the truncated pVHL.