{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T06:56:45Z","timestamp":1765609005955,"version":"build-2065373602"},"reference-count":54,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,6]],"date-time":"2023-08-06T00:00:00Z","timestamp":1691280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FSC 2014-2020 Project","award":["IS T3-AN-04"],"award-info":[{"award-number":["IS T3-AN-04"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, and it is typically caused by PKD1 and PKD2 heterozygous variants. Nonetheless, the extensive phenotypic variability observed among affected individuals, even within the same family, suggests a more complex pattern of inheritance. We describe an ADPKD family in which the proband presented with an earlier and more severe renal phenotype (clinical diagnosis at the age of 14 and end-stage renal disease aged 24), compared to the other affected family members. Next-generation sequencing (NGS)-based analysis of polycystic kidney disease (PKD)-associated genes in the proband revealed the presence of a pathogenic PKD2 variant and a likely pathogenic variant in PKD1, according to the American College of Medical Genetics and Genomics (ACMG) criteria. The PKD2 nonsense p.Arg872Ter variant was segregated from the proband\u2019s father, with a mild phenotype. A similar mild disease presentation was found in the proband\u2019s aunts and uncle (the father\u2019s siblings). The frameshift p.Asp3832ProfsTer128 novel variant within PKD1 carried by the proband in addition to the pathogenic PKD2 variant was not found in either parent. This report highlights that the co-inheritance of two or more PKD genes or alleles may explain the extensive phenotypic variability among affected family members, thus emphasizing the importance of NGS-based techniques in the definition of the prognostic course.<\/jats:p>","DOI":"10.3390\/genes14081589","type":"journal-article","created":{"date-parts":[[2023,8,6]],"date-time":"2023-08-06T10:01:53Z","timestamp":1691316113000},"page":"1589","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Co-Inheritance of Pathogenic Variants in PKD1 and PKD2 Genes Determined by Parental Segregation and De Novo Origin: A Case Report"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7217-7388","authenticated-orcid":false,"given":"Ludovico","family":"Graziani","sequence":"first","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2502-7157","authenticated-orcid":false,"given":"Stefania","family":"Zampatti","sequence":"additional","affiliation":[{"name":"Genomic Medicine Laboratory UILDM, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam Lucia","family":"Carriero","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8616-5065","authenticated-orcid":false,"given":"Chiara","family":"Minotti","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Peconi","sequence":"additional","affiliation":[{"name":"Genomic Medicine Laboratory UILDM, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Bengala","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Tor Vergata University Hospital, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emiliano","family":"Giardina","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"},{"name":"Genomic Medicine Laboratory UILDM, IRCCS Fondazione Santa Lucia, 00179 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7781-602X","authenticated-orcid":false,"given":"Giuseppe","family":"Novelli","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"},{"name":"Medical Genetics Unit, Tor Vergata University Hospital, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Elisakova, V., Merta, M., Reiterova, J., Baxova, A., Kotlas, J., Hirschfeldova, K., Obeidova, L., Tesar, V., and Stekrova, J. 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