Von Hippel-Lindau disease type 2 in a Chinese family with a VHL p.W88X truncation

Von Hippel-Lindau (VHL) disease is an autosomal dominant syndrome caused by germline mutations in the synonymous VHL gene encoding a tumor suppressor. Affected individuals are susceptible to various benign and malignant tumors. Based on the phenotypes, VHL disease is classified as type 1 and type 2. Here, we describe a Chinese family diagnosed as VHL disease type 2, with different metabolic status of tumors on FDG PET-CT. Genetic analysis revealed a germline c.264G > A point mutation, resulting in premature termination at codon 88 (p.W88X). This pedigree represents a rare link between p.W88X nonsense mutation (genotype) and VHL disease type 2 (phenotype), which has not been previously described. This is also the first nonsense mutation to manifest as VHL disease type 2 in ethnic Chinese. We also reviewed the literature and provided an outline of mutations associated with VHL disease in China.