{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:40:33Z","timestamp":1790642433779,"version":"4.1.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:p>\n                    Renal disease variability in autosomal dominant polycystic kidney disease (ADPKD) is strongly influenced by the gene locus (\n                    <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                    versus\n                    <jats:italic toggle=\"yes\">PKD2<\/jats:italic>\n                    ). Recent studies identified nontruncating\n                    <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                    mutations in approximately 30% of patients who underwent comprehensive mutation screening, but the clinical significance of these mutations is not well defined. We examined the genotype-renal function correlation in a prospective cohort of 220 unrelated ADPKD families ascertained through probands with serum creatinine \u22641.4 mg\/dl at recruitment. We screened these families for\n                    <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">PKD2<\/jats:italic>\n                    mutations and reviewed the clinical outcomes of the probands and affected family members. Height\u2013adjusted total kidney volume (htTKV) was obtained in 161 affected subjects. Multivariate Cox proportional hazard modeling for renal and patient survival was performed in 707 affected probands and family members. Overall, we identified pathogenic mutations in 84.5% of our families, in which the prevalence of\n                    <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                    truncating,\n                    <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                    in\u2013frame insertion\/deletion,\n                    <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                    nontruncating, and\n                    <jats:italic toggle=\"yes\">PKD2<\/jats:italic>\n                    mutations was 38.3%, 4.3%, 27.1%, and 30.3%, respectively. Compared with patients with\n                    <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                    truncating mutations, patients with\n                    <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                    in\u2013frame insertion\/deletion,\n                    <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                    nontruncating, or\n                    <jats:italic toggle=\"yes\">PKD2<\/jats:italic>\n                    mutations have smaller htTKV and reduced risks (hazard ratio [95% confidence interval]) of ESRD (0.35 [0.14 to 0.91], 0.10 [0.05 to 0.18], and 0.03 [0.01 to 0.05], respectively) and death (0.31 [0.11 to 0.87], 0.20 [0.11 to 0.38], and 0.18 [0.11 to 0.31], respectively). Refined genotype-renal disease correlation coupled with targeted next generation sequencing of\n                    <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">PKD2<\/jats:italic>\n                    may provide useful clinical prognostication for ADPKD.\n                  <\/jats:p>","DOI":"10.1681\/asn.2015060648","type":"journal-article","created":{"date-parts":[[2015,10,9]],"date-time":"2015-10-09T22:58:50Z","timestamp":1444431530000},"page":"1861-1868","source":"Crossref","is-referenced-by-count":154,"title":["Refining Genotype-Phenotype Correlation in Autosomal Dominant Polycystic Kidney Disease"],"prefix":"10.1681","volume":"27","author":[{"given":"Young-Hwan","family":"Hwang","sequence":"first","affiliation":[{"name":"Department of Medicine, Eulji General Hospital, Seoul, South Korea;"},{"name":"Division of Nephrology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Conklin","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, University Health Network and University of Toronto, Toronto, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winnie","family":"Chan","sequence":"additional","affiliation":[{"name":"Division of Nephrology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole M.","family":"Roslin","sequence":"additional","affiliation":[{"name":"Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jannel","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Nephrology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"He","sequence":"additional","affiliation":[{"name":"Division of Nephrology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kairong","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Nephrology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie L.","family":"Sundsbak","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina M.","family":"Heyer","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoom","family":"Haider","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, University Health Network and University of Toronto, Toronto, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Paterson","sequence":"additional","affiliation":[{"name":"Program in Genetics and Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Harris","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"York","family":"Pei","sequence":"additional","affiliation":[{"name":"Division of Nephrology and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2015,10,9]]},"reference":[{"issue":"Suppl 4","key":"B1-20230819","doi-asserted-by":"crossref","first-page":"iv15","DOI":"10.1093\/ndt\/gfu017","article-title":"Renal replacement therapy for autosomal dominant polycystic kidney disease (ADPKD) in Europe: Prevalence and survival\u2014an analysis of data from the ERA-EDTA Registry.","volume":"29","author":"Spithoven","year":"2014","journal-title":"Nephrol Dial Transplant"},{"key":"B2-20230819","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nrneph.2010.18","article-title":"Molecular diagnostics for autosomal dominant polycystic kidney disease.","volume":"6","author":"Harris","year":"2010","journal-title":"Nat Rev Nephrol"},{"key":"B3-20230819","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1159\/000421651","article-title":"Genetic heterogeneity of polycystic kidney disease in Europe.","volume":"97","author":"Peters","year":"1992","journal-title":"Contrib Nephrol"},{"key":"B4-20230819","doi-asserted-by":"crossref","first-page":"1833","DOI":"10.1681\/ASN.2009020162","article-title":"Family history of renal disease severity predicts the mutated gene in ADPKD.","volume":"20","author":"Barua","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"B5-20230819","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0140-6736(98)03495-3","article-title":"Comparison of phenotypes of polycystic kidney disease types 1 and 2. European PKD1-PKD2 Study Group.","volume":"353","author":"Hateboer","year":"1999","journal-title":"Lancet"},{"key":"B6-20230819","doi-asserted-by":"crossref","first-page":"710","DOI":"10.2215\/CJN.01581105","article-title":"Incident renal events and risk factors in autosomal dominant polycystic kidney disease: A population and family-based cohort followed for 22 years.","volume":"1","author":"Dicks","year":"2006","journal-title":"Clin J Am Soc Nephrol"},{"key":"B7-20230819","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1097\/01.ASN.0000061774.90975.25","article-title":"Genotype-renal function correlation in type 2 autosomal dominant polycystic kidney disease.","volume":"14","author":"Magistroni","year":"2003","journal-title":"J Am Soc Nephrol"},{"key":"B8-20230819","doi-asserted-by":"crossref","first-page":"3013","DOI":"10.1681\/ASN.2006080835","article-title":"Cyst number but not the rate of cystic growth is associated with the mutated gene in autosomal dominant polycystic kidney disease.","volume":"17","author":"Harris","year":"2006","journal-title":"J Am Soc Nephrol"},{"key":"B9-20230819","doi-asserted-by":"crossref","first-page":"2132","DOI":"10.1111\/j.1523-1755.2004.66003.x","article-title":"Comparison between siblings and twins supports a role for modifier genes in ADPKD.","volume":"66","author":"Persu","year":"2004","journal-title":"Kidney Int"},{"key":"B10-20230819","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1681\/ASN.2004090758","article-title":"Progressive loss of renal function is an age-dependent heritable trait in type 1 autosomal dominant polycystic kidney disease.","volume":"16","author":"Paterson","year":"2005","journal-title":"J Am Soc Nephrol"},{"key":"B11-20230819","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1111\/j.1523-1755.2005.00203.x","article-title":"Modifier genes play a significant role in the phenotypic expression of PKD1.","volume":"67","author":"Fain","year":"2005","journal-title":"Kidney Int"},{"key":"B12-20230819","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1681\/ASN.2006121387","article-title":"Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease.","volume":"18","author":"Rossetti","year":"2007","journal-title":"J Am Soc Nephrol"},{"key":"B13-20230819","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1038\/ki.2008.686","article-title":"Incompletely penetrant PKD1 alleles suggest a role for gene dosage in cyst initiation in polycystic kidney disease.","volume":"75","author":"Rossetti","year":"2009","journal-title":"Kidney Int"},{"key":"B14-20230819","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/ki.2011.370","article-title":"A missense mutation in PKD1 attenuates the severity of renal disease.","volume":"81","author":"Pei","year":"2012","journal-title":"Kidney Int"},{"key":"B15-20230819","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1681\/ASN.2012070650","article-title":"Type of PKD1 mutation influences renal outcome in ADPKD.","volume":"24","author":"Cornec-Le Gall","year":"2013","journal-title":"J Am Soc Nephrol"},{"key":"B16-20230819","doi-asserted-by":"crossref","first-page":"4257","DOI":"10.1172\/JCI64313","article-title":"Functional polycystin-1 dosage governs autosomal dominant polycystic kidney disease severity.","volume":"122","author":"Hopp","year":"2012","journal-title":"J Clin Invest"},{"key":"B17-20230819","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1056\/NEJMoa054341","article-title":"Volume progression in polycystic kidney disease.","volume":"354","author":"Grantham","year":"2006","journal-title":"N Engl J Med"},{"key":"B18-20230819","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations.","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat Methods"},{"key":"B19-20230819","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1101\/gr.176601","article-title":"Predicting deleterious amino acid substitutions.","volume":"11","author":"Ng","year":"2001","journal-title":"Genome Res"},{"key":"B20-20230819","doi-asserted-by":"crossref","first-page":"e46688","DOI":"10.1371\/journal.pone.0046688","article-title":"Predicting the functional effect of amino acid substitutions and indels.","volume":"7","author":"Choi","year":"2012","journal-title":"PLoS One"},{"key":"B21-20230819","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1086\/318188","article-title":"Bilineal disease and trans-heterozygotes in autosomal dominant polycystic kidney disease.","volume":"68","author":"Pei","year":"2001","journal-title":"Am J Hum 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ADPKD.","volume":"20","author":"Pei","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"B29-20230819","doi-asserted-by":"crossref","first-page":"e67","DOI":"10.1093\/nar\/gkp215","article-title":"Human Splicing Finder: An online bioinformatics tool to predict splicing signals.","volume":"37","author":"Desmet","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"B30-20230819","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1038\/ki.2008.485","article-title":"Characterization of large rearrangements in autosomal dominant polycystic kidney disease and the PKD1\/TSC2 contiguous gene syndrome.","volume":"74","author":"Consugar","year":"2008","journal-title":"Kidney Int"},{"key":"B31-20230819","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v047.i04","article-title":"Frailtypack: An R package for analysis of correlated survival data with Frailty models using penalized likelihood estimation or parametrical estimation.","volume":"47","author":"Rondeau","year":"2012","journal-title":"J Stat Softw"}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/00001751-201606000-00033","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:27:05Z","timestamp":1786130825000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00001751-201606000-00033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,9]]},"references-count":31,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2016]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.2015060648","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.725844103.793521829","asserted-by":"object"}]},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,10,9]]}}}