BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic renal disorder with an incidence of 1:1000. Mutations in two genes (PKD1 and PKD2) have been identified as causative. Eighty-five percent of patients with ADPKD carry their mutation in the PKD1 gene. So far, > 500 mutations for PKD1 and > 120 mutations for PKD2, respectively, are known. METHODS: In this study, we performed mutation analysis of PKD1 and PKD2 by exon sequencing in patients during routine molecular diagnostics for ADPKD. RESULTS: In total, 60 mutations were identified in 93 patients representing a mutation detection efficiency of 64.5%. Fifty-two mutations were identified in PKD1 (86.7%) and 8 in PKD2 (13.3%). These include 41 novel mutations detected in PKD1 and 5 novel mutations in PKD2. Accordingly, our data expand the spectrum of known PKD mutations by 8% for PKD1 (41/513) and 4.2% for PKD2 (5/120). These results are in agreement with the detection ranges of 42%, 63% and 64% for definitive disease-causing mutations, and 78%, 86% and 89% for all identified variants reported in several comprehensive mutation screening reports. CONCLUSIONS: The increased number of known mutations will facilitate future studies into genotype-phenotype correlations.
BACKGROUND:Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic renal disorder with an incidence of 1:1000. Mutations in two genes (PKD1 and PKD2) have been identified as causative. Eighty-five percent of patients with ADPKD carry their mutation in the PKD1 gene. So far, > 500 mutations for PKD1 and > 120 mutations for PKD2, respectively, are known. METHODS: In this study, we performed mutation analysis of PKD1 and PKD2 by exon sequencing in patients during routine molecular diagnostics for ADPKD. RESULTS: In total, 60 mutations were identified in 93 patients representing a mutation detection efficiency of 64.5%. Fifty-two mutations were identified in PKD1 (86.7%) and 8 in PKD2 (13.3%). These include 41 novel mutations detected in PKD1 and 5 novel mutations in PKD2. Accordingly, our data expand the spectrum of known PKD mutations by 8% for PKD1 (41/513) and 4.2% for PKD2 (5/120). These results are in agreement with the detection ranges of 42%, 63% and 64% for definitive disease-causing mutations, and 78%, 86% and 89% for all identified variants reported in several comprehensive mutation screening reports. CONCLUSIONS: The increased number of known mutations will facilitate future studies into genotype-phenotype correlations.
Authors: Sandro Rossetti; Katharina Hopp; Robert A Sikkink; Jamie L Sundsbak; Yean Kit Lee; Vickie Kubly; Bruce W Eckloff; Christopher J Ward; Christopher G Winearls; Vicente E Torres; Peter C Harris Journal: J Am Soc Nephrol Date: 2012-03-01 Impact factor: 10.121
Authors: Gnanasambandan Ramanathan; Santu Ghosh; Ramprasad Elumalai; Soundararajan Periyasamy; Bhaskar V K S Lakkakula Journal: Indian J Med Res Date: 2016-06 Impact factor: 2.375
Authors: Amali C Mallawaarachchi; Timothy J Furlong; John Shine; Peter C Harris; Mark J Cowley Journal: Genet Med Date: 2018-10-29 Impact factor: 8.822
Authors: Caroline Robinson; Thomas F Hiemstra; Deborah Spencer; Sarah Waller; Laura Daboo; Fiona E Karet Frankl; Richard N Sandford Journal: BMC Nephrol Date: 2012-08-03 Impact factor: 2.388