title: Novel mutations of PKD1 gene in Chinese patients with autosomal dominant polycystic kidney disease.
abstract: BACKGROUND
  Autosomal dominant polycystic kidney disease (ADPKD) is a common disease in China. The major gene responsible for ADPKD, PKD1, has been fully characterized and shown to encode an integral membrane protein, polycystin 1, which is thought to be involved in cell-cell and cell-matrix interaction. Until now, 82 mutations of PKD1 gene have been reported in European, American, and Asian populations. However, there has been no report on mutations of the PKD1 gene in a Chinese population.
  
  
  METHODS
  Eighty Chinese patients in 60 families with ADPKD were screened for mutations in the 3' region of the PKD1 gene using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and DNA-sequencing techniques.
  
  
  RESULTS
  Three mutations were found. The first mutation is a 12593delA frameshift mutation in exon 45, and the polycystin change is 4129WfsX4197, 107 amino acids shorter than the normal polycystin (4302aa). The second mutation is a 12470InsA frameshift mutation in exon 45, producing 4088DfsX4156, and the predicted protein is 148 amino acids shorter than the normal. The third one is a 11151C-->T transition in exon 37 converting Pro3648 to Leu. In addition, nine DNA variants, including IVS44delG, were identified.
  
  
  CONCLUSIONS
  Three mutations in Chinese ADPKD patients are described and all of them are de novo mutations. Data obtained from mutation analysis also suggests that the mutation rate of the 3' single-copy region of PKD1 in Chinese ADPKD patients is very low, and there are no mutation hot spots in the PKD1 gene. Mutations found in Chinese ADPKD patients, including nucleotide substitution and minor frameshift, are similar to the findings reported by other researchers. Many mutations of the PKD1 gene probably exist in the duplicated region, promoter region, and the introns of PKD1.
authors.affiliation: Department of Medical Genetics, West China Medical Center, Sichuan University, Sichuan Province, Chengdu 610041, People's Republic of China.
authors.forename: Lan
authors.initials: L
authors.lastname: Ding
authors.forename: Sizhong
authors.initials: S
authors.lastname: Zhang
authors.forename: Weimin
authors.initials: W
authors.lastname: Qiu
authors.forename: Cuiying
authors.initials: C
authors.lastname: Xiao
authors.forename: Shaoqing
authors.initials: S
authors.lastname: Wu
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Lu
authors.initials: L
authors.lastname: Cheng
authors.forename: Sixiao
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D050396:TRPP Cation Channels
chemical_list: D011506:Proteins; D050396:TRPP Cation Channels