title: Identification of novel PKD1 and PKD2 mutations in a Chinese population with autosomal dominant polycystic kidney disease.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most frequently inherited renal diseases caused by mutations in PKD1 and PKD2. We performed mutational analyses of PKD genes in 49 unrelated patients using direct PCR-sequencing and multiplex ligation-dependent probe amplification (MLPA) for PKD1 and PKD2. RT-PCR analysis was also performed in a family with a novel PKD2 splicing mutation. Disease-causing mutations were identified in 44 (89.8%) of the patients: 42 (95.5%) of the patients showed mutations in PKD1, and 2 (4.5%) showed mutations in PKD2. Ten nonsense, 17 frameshift, 4 splicing and one in-frame mutation were found in 32 of the patients. Large rearrangements were found in 3 patients, and missense mutations were found in 9 patients. Approximately 61.4% (27/44) of the mutations are first reported with a known mutation rate of 38.6%. RNA analysis of a novel PKD2 mutation (c.595_595 + 14delGGTAAGAGCGCGCGA) suggested monoallelic expression of the wild-type allele. Furthermore, patients with PKD1-truncating mutations reached end-stage renal disease (ESRD) earlier than patients with non-truncating mutations (47 ± 3.522 years vs. 59 ± 11.687 years, P = 0.016). The mutation screening of PKD genes in Chinese ADPKD patients will enrich our mutation database and significantly contribute to improve genetic counselling for ADPKD patients.
authors.affiliation: Women's Hospital School of Medicine Zhejiang University, Hangzhou 310006, P. R. China.|Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Hangzhou 310006, P. R. China.
authors.forename: Bei
authors.initials: B
authors.lastname: Liu
authors.affiliation: Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China.|The International Peace Maternity &Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P. R. China.
authors.forename: Song-Chang
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Women's Hospital School of Medicine Zhejiang University, Hangzhou 310006, P. R. China.|Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Hangzhou 310006, P. R. China.
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Yang
authors.affiliation: Women's Hospital School of Medicine Zhejiang University, Hangzhou 310006, P. R. China.|Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Hangzhou 310006, P. R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yan
authors.affiliation: Women's Hospital School of Medicine Zhejiang University, Hangzhou 310006, P. R. China.|Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Hangzhou 310006, P. R. China.
authors.forename: Ye-Qing
authors.initials: YQ
authors.lastname: Qian
authors.affiliation: Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China.|The International Peace Maternity &Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P. R. China.
authors.forename: Jun-Yu
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China.|The International Peace Maternity &Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P. R. China.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Hu
authors.affiliation: Women's Hospital School of Medicine Zhejiang University, Hangzhou 310006, P. R. China.|Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Hangzhou 310006, P. R. China.
authors.forename: Min-Yue
authors.initials: MY
authors.lastname: Dong
authors.affiliation: Women's Hospital School of Medicine Zhejiang University, Hangzhou 310006, P. R. China.|Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Hangzhou 310006, P. R. China.
authors.forename: Fan
authors.initials: F
authors.lastname: Jin
authors.affiliation: Women's Hospital School of Medicine Zhejiang University, Hangzhou 310006, P. R. China.|Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Hangzhou 310006, P. R. China.|Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China.|The International Peace Maternity &Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P. R. China.
authors.forename: He-Feng
authors.initials: HF
authors.lastname: Huang
authors.affiliation: Women's Hospital School of Medicine Zhejiang University, Hangzhou 310006, P. R. China.|Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Hangzhou 310006, P. R. China.|Institute of Embryo-Fetal Original Adult Disease Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China.|The International Peace Maternity &Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P. R. China.
authors.forename: Chen-Ming
authors.initials: CM
authors.lastname: Xu
mesh_terms: D000328:Adult; D017668:Age of Onset; D044466:Asian People / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics* / Q000401:mortality; D016133:Polymerase Chain Reaction; D050396:TRPP Cation Channels / Q000235:genetics*
chemical_list: D050396:TRPP Cation Channels