{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:44:17Z","timestamp":1790876657400,"version":"4.1.0"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2017,9]]},"abstract":"\n The absence of a positive family history (PFH) in 10%\u201325% of patients poses a diagnostic challenge for autosomal dominant polycystic kidney disease (ADPKD). In the Toronto Genetic Epidemiology Study of Polycystic Kidney Disease, 210 affected probands underwent renal function testing, abdominal imaging, and comprehensive\n PKD1<\/jats:italic>\n and\n PKD2<\/jats:italic>\n mutation screening. From this cohort, we reviewed all patients with and without an apparent family history, examined their parental medical records, and performed renal imaging in all available parents of unknown disease status. Subsequent reclassification of 209 analyzed patients revealed 72.2% (151 of 209) with a PFH, 15.3% (32 of 209) with\n de novo<\/jats:italic>\n disease, 10.5% (22 of 209) with an indeterminate family history, and 1.9% (four of 209) with PFH in retrospect. Among the patients with\n de novo<\/jats:italic>\n cases, we found two families with germline mosaicism and one family with somatic mosaicism. Additionally, analysis of renal imaging revealed that 16.3% (34 of 209) of patients displayed atypical PKD, most of which followed one of three patterns: asymmetric or focal PKD with PFH and an identified\n PKD1<\/jats:italic>\n or\n PKD2<\/jats:italic>\n mutation (15 of 34), asymmetric and\n de novo<\/jats:italic>\n PKD with proven or suspected somatic mosaicism (seven of 34), or focal PKD without any identifiable\n PKD1<\/jats:italic>\n or\n PKD2<\/jats:italic>\n mutation (eight of 34). In conclusion, PKD without an apparent family history may be due to\n de novo<\/jats:italic>\n disease, missing parental medical records, germline or somatic mosaicism, or mild disease from hypomorphic\n PKD1<\/jats:italic>\n and\n PKD2<\/jats:italic>\n mutations. Furthermore, mutations of a newly identified gene for ADPKD,\n GANAB<\/jats:italic>\n , and somatic mosaicism need to be considered in the mutation-negative patients with focal disease.\n <\/jats:p>","DOI":"10.1681\/asn.2016090938","type":"journal-article","created":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T20:40:23Z","timestamp":1495140023000},"page":"2768-2776","source":"Crossref","is-referenced-by-count":103,"title":["Polycystic Kidney Disease without an Apparent Family History"],"prefix":"10.1681","volume":"28","author":[{"given":"Ioan-Andrei","family":"Iliuta","sequence":"first","affiliation":[{"name":"Division of Nephrology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinusha","family":"Kalatharan","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":"Emilie","family":"Cornec-Le Gall","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota;"}],"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":"Marina","family":"Pourafkari","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, University Health Network and University of Toronto, Toronto, Ontario, Canada;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Ting","sequence":"additional","affiliation":[{"name":"Division of Nephrology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Nephrology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia C.","family":"Borgo","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":"Xuewen","family":"Song","sequence":"additional","affiliation":[{"name":"Division of Nephrology and"}],"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":"Sarah R.","family":"Senum","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Hwan","family":"Hwang","sequence":"additional","affiliation":[{"name":"Truewords Dialysis Clinic, Incheon, South Korea; and"}],"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"}],"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":"Korosh","family":"Khalili","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, University Health Network and University of Toronto, Toronto, Ontario, Canada;"}],"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":[[2017,5,18]]},"reference":[{"key":"B1-20230819","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.semnephrol.2010.06.002","article-title":"Diagnosis of autosomal-dominant polycystic kidney disease: An integrated approach.","volume":"30","author":"Barua","year":"2010","journal-title":"Semin Nephrol"},{"key":"B2-20230819","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/nrneph.2011.109","article-title":"Why kidneys fail in autosomal dominant polycystic kidney disease.","volume":"7","author":"Grantham","year":"2011","journal-title":"Nat Rev Nephrol"},{"key":"B3-20230819","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":"B4-20230819","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.1681\/ASN.2015050583","article-title":"Predicted mutation strength of non-truncating PKD1 mutations aids genotype-phenotype correlation in autosomal dominant polycystic kidney disease.","volume":"27","author":"Heyer","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"B5-20230819","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1681\/ASN.2015060648","article-title":"Refining genotype-phenotype correlation in autosomal dominant polycystic kidney disease.","volume":"27","author":"Hwang","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"B6-20230819","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1016\/j.ajhg.2016.05.004","article-title":"Mutations in GANAB, encoding the glucosidase II\u03b1 subunit, cause autosomal dominant polycystic kidney and liver disease.","volume":"98","author":"Porath","year":"2016","journal-title":"Am J Hum Genet"},{"key":"B7-20230819","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1681\/ASN.2008050507","article-title":"Unified criteria for ultrasonographic diagnosis of ADPKD.","volume":"20","author":"Pei","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"B8-20230819","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1681\/ASN.2014030297","article-title":"Imaging-based diagnosis of autosomal dominant polycystic kidney disease.","volume":"26","author":"Pei","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"B9-20230819","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1053\/j.ajkd.2008.05.015","article-title":"Presence of de novo mutations in autosomal dominant polycystic kidney disease patients without family history.","volume":"52","author":"Reed","year":"2008","journal-title":"Am J Kidney Dis"},{"key":"B10-20230819","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1681\/ASN.2013101138","article-title":"Imaging classification of autosomal dominant polycystic kidney disease: A simple model for selecting patients for clinical trials.","volume":"26","author":"Irazabal","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"B11-20230819","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1086\/316939","article-title":"Mutation analysis of the entire PKD1 gene: Genetic and diagnostic implications.","volume":"68","author":"Rossetti","year":"2001","journal-title":"Am J Hum Genet"},{"key":"B12-20230819","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":"B13-20230819","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/S0168-9525(00)02178-8","article-title":"Somatic mosaicism and variable expressivity.","volume":"17","author":"Gottlieb","year":"2001","journal-title":"Trends Genet"},{"key":"B14-20230819","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.3390\/genes5041064","article-title":"Somatic mosaicism in the human genome.","volume":"5","author":"Freed","year":"2014","journal-title":"Genes (Basel)"},{"key":"B15-20230819","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.tig.2015.03.013","article-title":"Somatic mosaicism: Implications for disease and transmission genetics.","volume":"31","author":"Campbell","year":"2015","journal-title":"Trends Genet"},{"key":"B16-20230819","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1681\/ASN.2011101032","article-title":"Identification of gene mutation in autosomal dominant polycystic kidney disease through targeted resequencing.","volume":"23","author":"Rossetti","year":"2012","journal-title":"J Am Soc Nephrol"},{"key":"B17-20230819","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":"B18-20230819","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/ki.2011.370","article-title":"Attenuated renal disease severity associated with a missense PKD1 mutation.","volume":"81","author":"Pei","year":"2012","journal-title":"Kidney Int"},{"key":"B19-20230819","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":"B20-20230819","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":"B21-20230819","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":"B22-20230819","doi-asserted-by":"crossref","first-page":"e46688","DOI":"10.1371\/journal.pone.0046688","article-title":"Predicting the functional effect of amino acid substitutions and 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