{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T02:36:41Z","timestamp":1792550201590,"version":"4.5.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T00:00:00Z","timestamp":1711324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by heterogeneous variants in the PKD1 and PKD2 genes. Genetic analysis of PKD1 has been challenging due to homology with 6 PKD1 pseudogenes and high GC content.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A single-tube multiplex long-range-PCR and long-read sequencing-based assay termed \u201ccomprehensive analysis of ADPKD\u201d (CAPKD) was developed and evaluated in 170 unrelated patients by comparing to control methods including next-generation sequencing (NGS) and multiplex ligation-dependent probe amplification.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>CAPKD achieved highly specific analysis of PKD1 with a residual noise ratio of 0.05% for the 6 pseudogenes combined. CAPKD identified PKD1 and PKD2 variants (ranging from variants of uncertain significance to pathogenic) in 160 out of the 170 patients, including 151 single-nucleotide variants (SNVs) and insertion-deletion variants (indels), 6 large deletions, and one large duplication. Compared to NGS, CAPKD additionally identified 2 PKD1 variants (c.78_96dup and c.10729_10732dup). Overall, CAPKD increased the rate of variant detection from 92.9% (158\/170) to 94.1% (160\/170), and the rate of diagnosis with pathogenic or likely pathogenic variants from 82.4% (140\/170) to 83.5% (142\/170). CAPKD also directly determined the cis-\/trans-configurations in 11 samples with 2 or 3 SNVs\/indels, and the breakpoints of 6 large deletions and one large duplication, including 2 breakpoints in the intron 21 AG-repeat of PKD1, which could only be correctly characterized by aligning to T2T-CHM13.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>CAPKD represents a comprehensive and specific assay toward full characterization of PKD1 and PKD2 variants, and improves the genetic diagnosis for ADPKD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/clinchem\/hvae030","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T01:48:43Z","timestamp":1708998523000},"page":"841-854","source":"Crossref","is-referenced-by-count":16,"title":["Comprehensive Analysis of <i>PKD1<\/i> and <i>PKD2<\/i> by Long-Read Sequencing in Autosomal Dominant Polycystic Kidney Disease"],"prefix":"10.1093","volume":"70","author":[{"given":"Dechao","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Nephrology, Changzheng Hospital, Naval Medical University , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Third-Generation Sequencing, Berry Genomics Corporation , Beijing , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Libao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Third-Generation Sequencing, Berry Genomics Corporation , Beijing , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Third-Generation Sequencing, Berry Genomics Corporation , Beijing , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyi","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Changzheng Hospital, Naval Medical University , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changlin","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Changzheng Hospital, Naval Medical University , Shanghai , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"2024060223533571900_hvae030-B1","doi-asserted-by":"crossref","first-page":"790","DOI":"10.2215\/CJN.02320220","article-title":"Insights into autosomal dominant polycystic kidney disease from genetic studies","volume":"16","author":"Lanktree","year":"2021","journal-title":"Clin J Am Soc 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