title: Molecular basis of von Hippel-Lindau syndrome in Chinese patients.
abstract: BACKGROUND
  Von Hippel-Lindau (VHL) syndrome is an autosomal dominant familial cancer syndrome predisposing the affected individuals to multiple tumours in various organs. The genetic basis of VHL in Southern Chinese is largely unknown. In this study, we characterized the mutation spectrum of VHL in nine unrelated Southern Chinese families.
  
  
  METHODS
  Nine probands with clinical features of VHL, two symptomatic and eight asymptomatic family members were included in this study. Prenatal diagnosis was performed twice for one proband. Two probands had only isolated bilateral phaeochromocytoma. The VHL gene was screened for mutations by polymerase chain reaction, direct sequencing and multiplex ligation-dependent probe amplification (MLPA).
  
  
  RESULTS
  The nine probands and the two symptomatic family members carried heterozygous germline mutations. Eight different VHL mutations were identified in the nine probands. One splicing mutation, NM_000551.2: c.463+1G > T, was novel. The other seven VHL mutations, c.233A > G [p.Asn78Ser], c.239G > T [p.Ser80Ile], c.319C > G [p.Arg107Gly], c.481C > T [p.Arg161X], c.482G > A [p.Arg161Gln], c.499C > T [p.Arg167Trp] and an exon 2 deletion, had been previously reported. Three asymptomatic family members were positive for the mutation and the other five tested negative. In prenatal diagnosis, the fetuses were positive for the mutation.
  
  
  CONCLUSIONS
  Genetic analysis could accurately confirm VHL syndrome in patients with isolated tumours such as sporadic phaeochromocytoma or epididymal papillary cystadenoma. Mutation detection in asymptomatic family members allows regular tumour surveillance and early intervention to improve their prognosis. DNA-based diagnosis can have an important impact on clinical management for VHL families.
authors.affiliation: Department of Pathology, Princess Margaret Hospital, Hong Kong, China.
authors.forename: Wai-Kwan
authors.initials: WK
authors.lastname: Siu
authors.forename: Ronald Ching-Wan
authors.initials: RC
authors.lastname: Ma
authors.forename: Ching-Wan
authors.initials: CW
authors.lastname: Lam
authors.forename: Chloe Miu
authors.initials: CM
authors.lastname: Mak
authors.forename: Yuet-Ping
authors.initials: YP
authors.lastname: Yuen
authors.forename: Fai-Man Ivan
authors.initials: FM
authors.lastname: Lo
authors.forename: Kin-Wah
authors.initials: KW
authors.lastname: Chan
authors.forename: Siu-Fung
authors.initials: SF
authors.lastname: Lam
authors.forename: Siu-Cheung
authors.initials: SC
authors.lastname: Ling
authors.forename: Sui-Fan
authors.initials: SF
authors.lastname: Tong
authors.forename: Wing-Yee
authors.initials: WY
authors.lastname: So
authors.forename: Chun-Chung
authors.initials: CC
authors.lastname: Chow
authors.forename: Mary Hoi-Yin
authors.initials: MH
authors.lastname: Tang
authors.forename: Wing-Hung
authors.initials: WH
authors.lastname: Tam
authors.forename: Albert Yan-Wo
authors.initials: AY
authors.lastname: Chan
mesh_terms: D044466:Asian People; D004252:DNA Mutational Analysis; D006801:Humans; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*; D006623:von Hippel-Lindau Disease / Q000235:genetics*
chemical_list: D051794:Von Hippel-Lindau Tumor Suppressor Protein