title: [Familial and genetic study in a large Chinese kindred with von Hippel-Lindau disease and gene mutation analysis].
abstract: OBJECTIVE
  To report the clinical characterization of a large Chinese kindred with von Hippel-Lindau (VHL) disease and to evaluate the role of VHL genetic testing in diagnosis of VHL disease and clinical screening for members in VHL disease family.
  
  
  METHODS
  A large kindred with VHL disease was studied. DNA extracted from peripheral blood was amplified by PCR to three exons of VHL gene in 27 members. PCR products were directly sequenced. The data on involvement of multi-organs in the VHL disease kindred were obtained by medical history taking and radiography.
  
  
  RESULTS
  There were 47 members in the four generations of the Chinese VHL kindred; among them, 18 members were patients with diagnostically proven VHL disease. Their clinical manifestations included: central nervous system(CNS) hemangioblastoma (n=5), renal cell carcinomas and CNS hemangioblastoma (n=3), renal cell carcinomas and retinal angiomas (n=3), renal cell carcinomas and multiple pancreatic cysts (n=1), renal cell carcinomas and retinal angiomas and multiple pancreatic cysts (n=2), renal cell carcinomas and CNS hemangioblastomas and multiple pancreatic cysts (n=1), and multiple pancreatic cysts and multiple renal cysts (n=1), and multiple pancreatic cysts (n=2). The common lesions of 18 patients in the large kindred were: renal cell carcinomas (56%), CNS hemangioblastomas(50%),retinal angiomas(28%), and multiple pancreatic cysts(39%). Of the 27 members who volunteered for genetic analysis, all 11 affected family patients who are still alive, including 9 affected family patients and 2 asymptomatic patients, presented a codon 78 from Asn to Ser change at nucleotide 446(A to G) in exon 1. Four members were carriers with the same VHL gene mutation. Two asymptomatic cases were initially diagnosed by genetic testing and subsequently confirmed by radiological imaging and surgery. Members not having the gene mutation had no clinical evidence of VHL disease.
  
  
  CONCLUSIONS
  The large Chinese kindred with VHL disease was classified as type   . The main characteristics of the kindred are higher incidence of renal cell carcinomas and lower incidence of retinal angiomas. The genetic testing played an important role in early detecting asymptomatic patients and the carriers in clinical screening for members in the VHL families. Also, it is important to prevent the transmission of VHL disease to the offspring in the kindred.
authors.affiliation: Department of Urology, Renji Hospital, Shanghai Second Medical University, Shanghai, 200127 PR China. zj953@yahoo.com.cn
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Yi-ran
authors.initials: YR
authors.lastname: Huang
authors.forename: Jing-ding
authors.initials: JD
authors.lastname: Wang
authors.forename: Xiao-dong
authors.initials: XD
authors.lastname: Fan
mesh_terms: D001483:Base Sequence; D002681:China; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D006623:von Hippel-Lindau Disease / Q000145:classification / Q000175:diagnosis / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; D004247:DNA; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human