{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:39:22Z","timestamp":1783575562816,"version":"3.55.0"},"reference-count":12,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,12,24]],"date-time":"2020-12-24T00:00:00Z","timestamp":1608768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007375","name":"Associazione Emma e Ernesto Rulfo per la Genetica Medica","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007375","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Alport\u00a0syndrome (ATS) is a hereditary progressive hematuric nephropathy associated with sensorineural deafness and ocular abnormalities, which is caused by mutations in the <jats:italic>COL4A5<\/jats:italic> gene (X\u2010linked ATS) and in two autosomal genes, <jats:italic>COL4A4<\/jats:italic> and <jats:italic>COL4A3<\/jats:italic>, responsible of both recessive ATS and, when present in heterozygosity, of a spectrum of phenotypes ranging from isolated hematuria to frank renal disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Retrospective analysis of the clinical and genetic features of 76 patients from 34 unrelated ATS families (11 with mutations in <jats:italic>COL4A5<\/jats:italic>, 11 in <jats:italic>COL4A3<\/jats:italic>, and 12 in <jats:italic>COL4A4<\/jats:italic>) and genotype\/phenotype correlation for the <jats:italic>COL4A3<\/jats:italic>\/<jats:italic>COL4A4<\/jats:italic> heterozygotes (34 patients from 14 families).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eight (24%) of the 34 heterozygous <jats:italic>COL4A3<\/jats:italic> and <jats:italic>COL4A4<\/jats:italic> carriers developed renal failure at a mean age of 57\u00a0years, with a significantly lower risk than hemizygous <jats:italic>COL4A5<\/jats:italic> or double heterozygous <jats:italic>COL4A3<\/jats:italic>\/<jats:italic>COL4A4<\/jats:italic> carriers (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.01), but not different from that of the heterozygous <jats:italic>COL4A5<\/jats:italic> females (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.6). Heterozygous carriers of frameshift\/splicing variants in <jats:italic>COL4A3<\/jats:italic>\/<jats:italic>COL4A4<\/jats:italic> presented a higher risk of developing renal failure than those with missense variants in the glycine domains (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.015).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The renal functional prognosis of patients with <jats:italic>COL4A3<\/jats:italic>\/<jats:italic>COL4A4<\/jats:italic>\u2010positive ATS recapitulates that of the X\u2010linked ATS forms, with differences between heterozygous vs. double heterozygous patients and between carriers of loss\u2010of\u2010function vs. missense variants.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1576","type":"journal-article","created":{"date-parts":[[2020,12,25]],"date-time":"2020-12-25T07:14:38Z","timestamp":1608880478000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Deciphering the pathogenesis of the COL4\u2010related hematuric nephritis: A genotype\/phenotype study"],"prefix":"10.1002","volume":"9","author":[{"given":"Vera","family":"Uliana","sequence":"first","affiliation":[{"name":"Medical Genetics University Hospital of Parma Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Sebastio","sequence":"additional","affiliation":[{"name":"Medical Genetics University Hospital of Parma Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Riva","sequence":"additional","affiliation":[{"name":"Medical Genetics Department of Medicine and Surgery University of Parma Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Carli","sequence":"additional","affiliation":[{"name":"Medical Genetics University Hospital \u201cCitt\u00e0 della Salute\u201d Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Ruberto","sequence":"additional","affiliation":[{"name":"Pediatrics University Hospital of Parma Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Bianchi","sequence":"additional","affiliation":[{"name":"Pediatrics University Hospital of Parma Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Graziano","sequence":"additional","affiliation":[{"name":"Medical Genetics S. Orsola\u2010Malpighi University Hospital Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Capelli","sequence":"additional","affiliation":[{"name":"Nephrology S. Orsola\u2010Malpighi University Hospital Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio","family":"Faletra","sequence":"additional","affiliation":[{"name":"Medical Genetics I.R.C.C.S. 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