{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T04:30:02Z","timestamp":1793248202339,"version":"4.5.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["Can-SOLVE CKD Network Program"],"award-info":[{"award-number":["Can-SOLVE CKD Network Program"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000191","name":"Kidney Foundation of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000191","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015452","name":"Canadian Society of Nephrology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015452","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:p>\n                    Autosomal dominant polycystic kidney disease is the most common monogenic cause of ESKD. Genetic studies from patients and animal models have informed disease pathobiology and strongly support a \u201cthreshold model\u201d in which cyst formation is triggered by reduced functional polycystin dosage below a critical threshold within individual tubular epithelial cells due to (\n                    <jats:italic toggle=\"yes\">1<\/jats:italic>\n                    ) germline and somatic\n                    <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                    and\/or\n                    <jats:italic toggle=\"yes\">PKD2<\/jats:italic>\n                    mutations, (\n                    <jats:italic toggle=\"yes\">2<\/jats:italic>\n                    ) mutations of genes (\n                    <jats:italic toggle=\"yes\">e.g.<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">SEC63<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">SEC61B<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">GANAB<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">PRKCSH<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">DNAJB11<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">ALG8<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">ALG9<\/jats:italic>\n                    ) in the endoplasmic reticulum protein biosynthetic pathway, or (\n                    <jats:italic toggle=\"yes\">3<\/jats:italic>\n                    ) somatic mosaicism. Genetic testing has the potential to provide diagnostic and prognostic information in cystic kidney disease. However, mutation screening of\n                    <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                    is challenging due to its large size and complexity, making it both costly and labor intensive. Moreover, conventional Sanger sequencing\u2013based genetic testing is currently limited in elucidating the causes of atypical polycystic kidney disease, such as within-family disease discordance, atypical kidney imaging patterns, and discordant disease severity between total kidney volume and rate of eGFR decline. In addition, environmental factors, genetic modifiers, and somatic mosaicism also contribute to disease variability, further limiting prognostication by mutation class in individual patients. Recent innovations in next-generation sequencing are poised to transform and extend molecular diagnostics at reasonable costs. By comprehensive screening of multiple cystic disease and modifier genes, targeted gene panel, whole-exome, or whole-genome sequencing is expected to improve both diagnostic and prognostic accuracy to advance personalized medicine in autosomal dominant polycystic kidney disease.\n                  <\/jats:p>","DOI":"10.2215\/cjn.02320220","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T22:15:15Z","timestamp":1595283315000},"page":"790-799","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":141,"title":["Insights into Autosomal Dominant Polycystic Kidney Disease from Genetic Studies"],"prefix":"10.2215","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5750-6286","authenticated-orcid":false,"given":"Matthew B.","family":"Lanktree","sequence":"first","affiliation":[{"name":"Division of Nephrology, St. Joseph Healthcare Hamilton and Department of Medicine, McMaster 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