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ADPKD genetic diagnosis is complicated by <jats:italic>PKD1<\/jats:italic> pseudogenes located proximal to the original gene with a high degree of homology. The next generation sequencing (NGS) technology including whole exome sequencing (WES) and whole genome sequencing (WGS), is becoming more affordable and its use in the detection of ADPKD mutations for diagnostic and research purposes more widespread. However, how well does NGS technology compare with the Gold standard (Sanger sequencing) in the detection of ADPKD mutations? Is a question that remains to be answered. We have evaluated the efficacy of WES, WGS and targeted enrichment methodologies in detecting ADPKD mutations in the <jats:italic>PKD1<\/jats:italic> and <jats:italic>PKD2<\/jats:italic> genes in patients who were clinically evaluated by ultrasonography and renal function tests. Our results showed that WES detected <jats:italic>PKD1<\/jats:italic> mutations in ADPKD patients with 50% sensitivity, as the reading depth and sequencing quality were low in the duplicated regions of PKD1 (exons 1\u201332) compared with those of WGS and target enrichment arrays. Our investigation highlights major limitations of WES in ADPKD genetic diagnosis. Enhancing reading depth, quality and sensitivity of WES in the <jats:italic>PKD1<\/jats:italic> duplicated regions (exons 1\u201332) is crucial for its potential diagnostic or research applications.<\/jats:p>","DOI":"10.1038\/s41598-019-40761-w","type":"journal-article","created":{"date-parts":[[2019,3,11]],"date-time":"2019-03-11T11:03:05Z","timestamp":1552302185000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["PKD1 Duplicated regions limit clinical Utility of Whole Exome Sequencing for Genetic Diagnosis of Autosomal Dominant Polycystic Kidney Disease"],"prefix":"10.1038","volume":"9","author":[{"given":"Hamad","family":"Ali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahd","family":"Al-Mulla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naser","family":"Hussain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Medhat","family":"Naim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5212-4553","authenticated-orcid":false,"given":"Akram M.","family":"Asbeutah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"AlSahow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8357-1252","authenticated-orcid":false,"given":"Mohamed","family":"Abu-Farha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jehad","family":"Abubaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashraf","family":"Al Madhoun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajjad","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,11]]},"reference":[{"key":"40761_CR1","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1111\/j.1523-1755.2005.00201.x","volume":"67","author":"AC Ong","year":"2005","unstructured":"Ong, A. 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