title: Clinical and molecular characteristics of East Asian patients with von Hippel-Lindau syndrome.
abstract: BACKGROUND
  Von 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.
  
  
  METHODS
  To 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.
  
  
  RESULTS
  Of 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.
  
  
  CONCLUSIONS
  Evidence 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.
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 169610, Singapore.
authors.forename: Meihua
authors.initials: M
authors.lastname: Wong
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore, 138669, Singapore.
authors.forename: Ying-Hsia
authors.initials: YH
authors.lastname: Chu
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 169610, Singapore.
authors.forename: Hwei Ling
authors.initials: HL
authors.lastname: Tan
authors.affiliation: Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0374, Japan.
authors.forename: Hideharu
authors.initials: H
authors.lastname: Bessho
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 169610, Singapore.
authors.forename: Joanne
authors.initials: J
authors.lastname: Ngeow
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 169610, Singapore.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Tang
authors.affiliation: Division of Medical Oncology, National Cancer Centre Singapore, Singapore, 169610, Singapore. minhan.tan@gmail.com.|Institute of Bioengineering and Nanotechnology, Singapore, 138669, Singapore. minhan.tan@gmail.com.
authors.forename: Min-Han
authors.initials: MH
authors.lastname: Tan
mesh_terms: D005202:Asia, Eastern; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D012307:Risk Factors; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*; D006623:von Hippel-Lindau Disease / Q000235:genetics* / Q000473:pathology
chemical_list: D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human
keywords: Renal cell carcinoma; Retinal capillary hemangioblastoma; Von Hippel–Lindau syndrome