title: Mutation analysis in PKD1 of Japanese autosomal dominant polycystic kidney disease patients.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic renal disorder (incidence, 1:1,000). The mutation of PKD1 is thought to account for 85% of ADPKD. Although a considerable number of studies on PKD1 mutation have been published recently, most of them concern Caucasian ADPKD patients. In the present study, we examined PKD1 mutations in Japanese ADPKD patients. Long-range polymerase chain reaction (LR-PCR) with PKD1-specific primers followed by nested PCR was used to analyze the duplicated region of PKD1. Six novel chain-terminating mutations were detected: three nonsense mutations (Q2014X transition in exon 15, Q2969X in exon 24, and E2810X in exon 23), two deletions (2132del29 in exon10 and 7024delAC in exon 15), and one splicing mutation (IVS21-2delAG). There was also one nonconservative missense mutation (T2083I). Two other potentially pathogenic missense mutations (G2814R and L2816P) were on the downstream site of one nonsense mutation. These three mutations and a following polymorphism (8662C>T) were probably the result of gene conversion from one of the homologous genes to PKD1. Six other polymorphisms were found. Most PKD1 mutations in Japanese ADPKD patients were novel and definitely pathogenic. One pedigree did not link to either PKD1 or PKD2.
authors: Department of Environmental and Health Sciences, Kyoto University School of Public Health, Kyoto, Japan.
authors: Sumiko
authors: S
authors: Inoue
authors: Kayoko
authors: K
authors: Inoue
authors: Maki
authors: M
authors: Utsunomiya
authors: Jun-Ichi
authors: J
authors: Nozaki
authors: Yuichiro
authors: Y
authors: Yamada
authors: Toshio
authors: T
authors: Iwasa
authors: Eitaro
authors: E
authors: Mori
authors: Takeo
authors: T
authors: Yoshinaga
authors: Akio
authors: A
authors: Koizumi
mesh_terms: D000293:Adolescent; D000328:Adult; D015220:Calcium Channels / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D050396:TRPP Cation Channels
chemical_list: D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D011506:Proteins; D050396:TRPP Cation Channels