{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T21:27:54Z","timestamp":1782682074109,"version":"3.54.5"},"reference-count":31,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T00:00:00Z","timestamp":1655424000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Caroli disease (CD, OMIM #600643) is a rare autosomal recessive disorder characterized by polycystic segmental dilatation of the intrahepatic bile ducts and extreme variability in age of onset and clinical manifestations. When congenital hepatic fibrosis is associated with the polycystic dilatation of the biliary tract, the condition is referred as Caroli syndrome. The disease is thought to be caused by pathogenic variants in the <jats:italic>PKHD1<\/jats:italic> gene (OMIM *606702).<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We report the clinical, biochemical, and molecular characterization of three patients with a clinical suspicion of CS belonging to two different families. The genetic screening was performed using a target custom panel and sequencing was performed on Illumina platform.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetic analysis revealed the presence of rare variants in the <jats:italic>PKHD1<\/jats:italic> gene of the analyzed patients. In the first case, and his younger sister, two pathogenic variants (c.2702A&gt;C and c.4870C&gt;T) were found to be associated with a hepatic phenotype at clinical onset, followed by renal disease probably age\u2010related; while in the second case, one pathogenic variant (c.5879C&gt;G) and a complex allele with uncertain clinical significance [c.3407A&gt;G; c.8345G&gt;C; c.8606C&gt;A] were found to be associated with a severe hepatic phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The identification of the genetic causes of the disease and their relationship with the clinical phenotype could have a favorable impact on clinical management and complication prevention.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1998","type":"journal-article","created":{"date-parts":[[2022,6,18]],"date-time":"2022-06-18T05:38:53Z","timestamp":1655530733000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Rare variants in <i>PKHD1<\/i> associated with Caroli syndrome: Two case reports"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6422-3989","authenticated-orcid":false,"given":"Carola","family":"Giacobbe","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology University of Naples Federico II and CEINGE S.C.a r.l. Advanced Biotechnology  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Di Dato","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Science, Section of Pediatrics University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Palma","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology University of Naples Federico II and CEINGE S.C.a r.l. Advanced Biotechnology  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Amitrano","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Science University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Iorio","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Science, Section of Pediatrics University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2209-383X","authenticated-orcid":false,"given":"Giuliana","family":"Fortunato","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology University of Naples Federico II and CEINGE S.C.a r.l. 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