Abstract
BackgroundVon Hippel–Lindau (VHL) syndrome is a dominantly inherited multisystem cancer syndrome caused by a heterozygous mutation in the VHL tumor suppressor gene. Previous studies suggested that similar populations of Caucasian and Japanese patients have similar genotype or phenotype characteristics. In this comprehensive study of East Asian patients, we investigated the genetic and clinical characteristics of patients with VHL syndrome.MethodsTo create a registry of clinical characteristics and mutations reported in East Asian patients with VHL syndrome, we conducted a comprehensive review of English language and non-English language articles identified through a literature search. Publications in Japanese or Chinese language were read by native speakers of the language, who then performed the data extraction.ResultsOf 237 East Asian patients with VHL syndrome, 154 unique kindreds were identified for analysis. Analyzed by kindred, missense mutations were the most common (40.9%, 63/154), followed by large/complete deletions (32.5%, 50/154) and nonsense mutations (11.7%, 18/154). Compared with a previously reported study of both East Asian and non-East Asian patients, we found several key differences. First, missense and frameshift mutations in the VHL gene occurred less commonly in our population of East Asian patients (40.9% vs. 52.0%; P = 0.012 and 8.4% vs. 13.0%; P < 0.001, respectively). Second, large/complete deletions were more common in our population of East Asian patients (32.5% vs. 10.5%; P < 0.001). Third, phenotypically, we observed that, in our population of East Asian patients with VHL syndrome, the incidence of retinal capillary hemangioblastoma was lower, whereas the incidence of renal cell carcinoma was higher.ConclusionsEvidence suggests that the genotypic and phenotypic characteristics of East Asian patients with VHL syndrome differ from other populations. This should be considered when making screening recommendations for VHL syndrome in Asia.Electronic supplementary materialThe online version of this article (doi:10.1186/s40880-016-0141-z) contains supplementary material, which is available to authorized users.
Highlights
Von Hippel–Lindau (VHL) syndrome is a dominantly inherited multisystem cancer syndrome caused by a heterozygous mutation in the VHL tumor suppressor gene
Von Hippel–Lindau syndrome is transmitted in an autosomal dominant fashion and has a penetrance reported to exceed 90% by 60 years of age [4]
PCCs associated with VHL syndrome We found that 89.5% (17 of 19) of East Asian kindreds who developed PCC had an underlying missense mutation
Summary
Von Hippel–Lindau (VHL) syndrome is a dominantly inherited multisystem cancer syndrome caused by a heterozygous mutation in the VHL tumor suppressor gene. Von Hippel–Lindau (VHL) syndrome is an inherited multisystem cancer syndrome with an estimated incidence of 1 in 36,000 live births [1]. Those affected are predisposed to a spectrum of benign and malignant. Von Hippel–Lindau syndrome is transmitted in an autosomal dominant fashion and has a penetrance reported to exceed 90% by 60 years of age [4] It is caused by germline mutations in the VHL tumor suppressor gene, located on the short arm of chromosome 3. PVHL binds directly to hypoxia-inducible factor (HIF) [6] and targets the HIF alpha subunit for oxygen-dependent proteolysis [7]
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