title: Mutation analysis of autosomal dominant polycystic kidney disease genes in Han Chinese.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in two genes, PKD1 and PKD2. The complexity of these genes, particularly PKD1, has complicated genetic screening, though recent advances have provided new opportunities for amplifying these genes. In the Han Chinese population, no complete mutational analysis has previously been conducted across the entire span of PKD1 and PKD2. Here, we used single-strand conformation polymorphism (SSCP) analysis to screen the entire coding sequence of PKD1 and PKD2 in 85 healthy controls and 72 Han Chinese from 24 ADPKD pedigrees. In addition to 11 normal variants, we identified 17 mutations (12 in PKD1 and 5 in PKD2), 15 of which were novel ones (11 for PKD1 and 4 for PKD2). We did not identify any seeming mutational hot spots in PKD1 and PKD2. Notably, we found several disease-associated C-T or G-A mutations that led to charge or hydrophobicity changes in the corresponding amino acids. This suggests that the mutations cause conformational alterations in the PKD1 and PKD2 protein products that may impact the normal protein functions. Our study is the first report of screenable mutations in the full-length PKD1 and PKD2 genes of the Han Chinese, and also offers a benchmark for comparisons between Caucasian and Han ADPKD pedigrees and patients.
authors.affiliation: Division of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Shuzhong
authors.initials: S
authors.lastname: Zhang
authors.forename: Changlin
authors.initials: C
authors.lastname: Mei
authors.forename: Dianyong
authors.initials: D
authors.lastname: Zhang
authors.forename: Bing
authors.initials: B
authors.lastname: Dai
authors.forename: Bing
authors.initials: B
authors.lastname: Tang
authors.forename: Tianmei
authors.initials: T
authors.lastname: Sun
authors.forename: Haidan
authors.initials: H
authors.lastname: Zhao
authors.forename: Yukun
authors.initials: Y
authors.lastname: Zhou
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Yumei
authors.initials: Y
authors.lastname: Wu
authors.forename: Wenjing
authors.initials: W
authors.lastname: Wang
authors.forename: Xuefei
authors.initials: X
authors.lastname: Shen
authors.forename: Ji
authors.initials: J
authors.lastname: Song
mesh_terms: D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D002681:China / Q000208:ethnology; D004252:DNA Mutational Analysis; D005260:Female; D005784:Gene Amplification; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016891:Polycystic Kidney, Autosomal Dominant / Q000208:ethnology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011487:Protein Conformation; D000091283:Protein Kinase D2; D011494:Protein Kinases / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012016:Reference Values; D050396:TRPP Cation Channels
chemical_list: D000091283:Protein Kinase D2; D011494:Protein Kinases; D011506:Proteins; D050396:TRPP Cation Channels