2015
DOI: 10.1371/journal.pone.0116680
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An Efficient and Comprehensive Strategy for Genetic Diagnostics of Polycystic Kidney Disease

Abstract: Renal cysts are clinically and genetically heterogeneous conditions. Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent life-threatening genetic disease and mainly caused by mutations in PKD1. The presence of six PKD1 pseudogenes and tremendous allelic heterogeneity make molecular genetic testing challenging requiring laborious locus-specific amplification. Increasing evidence suggests a major role for PKD1 in early and severe cases of ADPKD and some patients with a recessive form. Furth… Show more

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Cited by 69 publications
(63 citation statements)
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“…11,12 As three of these exons fall outside of the pseudogene region, we attribute this lower sequencing depth to GC content rather than homology to the pseudogenes. Reduced coverage due to high GC content is likely due to PCR amplification bias during library creation and clonal amplification on the flowcell surface.…”
Section: Discussionmentioning
confidence: 99%
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“…11,12 As three of these exons fall outside of the pseudogene region, we attribute this lower sequencing depth to GC content rather than homology to the pseudogenes. Reduced coverage due to high GC content is likely due to PCR amplification bias during library creation and clonal amplification on the flowcell surface.…”
Section: Discussionmentioning
confidence: 99%
“…5,[10][11][12] An amplicon-based strategy using LR-PCR amplification of PKD1 and PKD2 exons, followed by MPS obtained a diagnostic rate of~60% in cohorts selected using only imaging criteria (ie, for whom a diseasecausing variant was not already known). 5,[10][11][12] These techniques are laborious and the PCR amplification process is error prone. Capturebased strategies have been trialled, to enrich for PKD1 and PKD2 exons, and in a small discovery cohort (n = 12) the diagnostic rate was 83%.…”
Section: Introductionmentioning
confidence: 99%
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“…However, optimization of targeted sequence capture approaches or the methodological advantages of WGS now allow mutation analysis by NGS of even highly confounding loci such as PKD1 [30]. NGS approaches are nowadays the gold standard for genetic screening for ADPKD and should encompass a number of other genes besides the ones discussed above such as GANAB or HNF1ÎČ that were recently described to be mutated in a subset of patients with ADPKD [31].…”
Section: Autosomal Dominant Pkdmentioning
confidence: 99%
“…A further 1330 patients with a PKD phenotype (n=525) or a nephronopthisis (NPHP)-related complex ciliopathy (n=805) were analyzed by nextgeneration sequencing (NGS), mainly targeted multi-gene panel testing 16 . Thereby, we identified different homozygous protein truncating DZIP1L mutations (c.463C>T; (p.Gln155 * ) and c.1061_1062del; (p.Glu354Alafs * 39)) in two additional unrelated consanguineous pedigrees, B155 and B8031, with hallmarks of ARPKD (Fig.…”
Section: Dzip1l Is a New Arpkd Genementioning
confidence: 99%