title: Identification of novel mutations in Chinese Hans with autosomal dominant polycystic kidney disease.
abstract: BACKGROUND
  Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease with an incidence of 1 in 400 to 1000. The disease is genetically heterogeneous, with two genes identified: PKD1 (16p13.3) and PKD2 (4q21). Molecular diagnosis of the disease in at-risk individuals is complicated due to the structural complexity of PKD1 gene and the high diversity of the mutations. This study is the first systematic ADPKD mutation analysis of both PKD1 and PKD2 genes in Chinese patients using denaturing high-performance liquid chromatography (DHPLC).
  
  
  METHODS
  Both PKD1 and PKD2 genes were mutation screened in each proband from 65 families using DHPLC followed by DNA sequencing. Novel variations found in the probands were checked in their family members available and 100 unrelated normal controls. Then the pathogenic potential of the variations of unknown significance was examined by evolutionary comparison, effects of amino acid substitutions on protein structure, and effects of splice site alterations using online mutation prediction resources.
  
  
  RESULTS
  A total of 92 variations were identified, including 27 reported previously. Definitely pathogenic mutations (ten frameshift, ten nonsense, two splicing defects and one duplication) were identified in 28 families, and probably pathogenic mutations were found in an additional six families, giving a total detection level of 52.3% (34/65). About 69% (20/29) of the mutations are first reported with a recurrent mutation rate of 31%.
  
  
  CONCLUSIONS
  Mutation study of PKD1 and PKD2 genes in Chinese Hans with ADPKD may contribute to a better understanding of the genetic diversity between different ethnic groups and enrich the mutation database. Besides, evaluating the pathogenic potential of novel variations should also facilitate the clinical diagnosis and genetic counseling of the disease.
authors.affiliation: Department of Medical Genetics, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Chaowen
authors.initials: C
authors.lastname: Yu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Zou
authors.forename: Zhangxue
authors.initials: Z
authors.lastname: Hu
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Yunqiang
authors.initials: Y
authors.lastname: Liu
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Ma
authors.forename: Mingyi
authors.initials: M
authors.lastname: Ma
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.forename: Sizhong
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D005820:Genetic Testing; D006801:Humans; D009154:Mutation / Q000235:genetics*; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*; D011487:Protein Conformation; D050396:TRPP Cation Channels / Q000235:genetics*
chemical_list: D050396:TRPP Cation Channels