{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:44:02Z","timestamp":1790876642609,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Pathogenic variants in type IV collagen genes (COL4A3, COL4A4, COL4A5) are classically associated with Alport syndrome (AS), a hereditary nephropathy primarily affecting the glomerular basement membrane (GBM). Recent findings, however, suggest a broader phenotypic spectrum that includes renal cyst formation, raising questions about overlapping mechanisms with other cystic kidney diseases. Clinically, renal cysts have been increasingly reported in patients with autosomal dominant and X-linked forms of Alport syndrome, particularly in association with glycine missense variants. The most recent studies focusing on the cystic phenotype in Alport syndrome provide growing support for the idea that variants in type IV collagen genes are associated with an increased likelihood of developing renal cysts, likely through mechanisms involving the structural integrity of renal basement membranes. In this review, we explore evidence from murine models and human studies indicating defects in collagen IV and discuss their contribution to cystogenesis. These observations underscore the need for broader genetic screening strategies and further investigation into the molecular mechanisms underlying this emerging phenotype.<\/jats:p>","DOI":"10.3390\/genes16060642","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T12:28:42Z","timestamp":1748435322000},"page":"642","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Collagen Type IV Variants and Kidney Cysts: Decoding the COL4A Puzzle"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9008-9368","authenticated-orcid":false,"given":"Matteo","family":"Rigato","sequence":"first","affiliation":[{"name":"Department of Nephrology, Dialysis and Transplantation, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"},{"name":"The International Renal Research Institute of Vicenza (IRRIV) Foundation, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6945-4460","authenticated-orcid":false,"given":"Carlotta","family":"Caprara","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Dialysis and Transplantation, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"},{"name":"The International Renal Research Institute of Vicenza (IRRIV) Foundation, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"},{"name":"Department of Medical Genetics and Genomics, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Said","family":"Cabrera-Aguilar","sequence":"additional","affiliation":[{"name":"The International Renal Research Institute of Vicenza (IRRIV) Foundation, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"},{"name":"Nephrology Service, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara 44200, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9225-4036","authenticated-orcid":false,"given":"Nenzi","family":"Marzano","sequence":"additional","affiliation":[{"name":"The International Renal Research Institute of Vicenza (IRRIV) Foundation, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Giuliani","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Dialysis and Transplantation, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"},{"name":"The International Renal Research Institute of Vicenza (IRRIV) Foundation, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7000-4907","authenticated-orcid":false,"given":"Barbara","family":"Mancini","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Genomics, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiorella","family":"Gastaldon","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Dialysis and Transplantation, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"},{"name":"The International Renal Research Institute of Vicenza (IRRIV) Foundation, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6697-4065","authenticated-orcid":false,"given":"Claudio","family":"Ronco","sequence":"additional","affiliation":[{"name":"The International Renal Research Institute of Vicenza (IRRIV) Foundation, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Zanella","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Dialysis and Transplantation, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"},{"name":"The International Renal Research Institute of Vicenza (IRRIV) Foundation, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5826-6715","authenticated-orcid":false,"given":"Daniela","family":"Zuccarello","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Genomics, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Corradi","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Dialysis and Transplantation, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"},{"name":"The International Renal Research Institute of Vicenza (IRRIV) Foundation, AULSS8 BERICA, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1007\/s11255-021-03065-5","article-title":"Prevalence, Risk Factors and Clinical Characteristics of Renal Dysfunction in Chinese Outpatients with Growth Simple Renal Cysts","volume":"54","author":"Wu","year":"2022","journal-title":"Int. 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