{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:37:13Z","timestamp":1780472233904,"version":"3.54.1"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,11,10]],"date-time":"2014-11-10T00:00:00Z","timestamp":1415577600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Portuguese Society of Nephrology"},{"name":"Unit of Research & Development in Nephrology","award":["FCT-725"],"award-info":[{"award-number":["FCT-725"]}]},{"name":"S\u00e3o Jo\u00e3o Hospital Centre"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2015,11]]},"abstract":"Alport syndrome (AS<\/jats:styled-content>) is caused by pathogenic mutations in the genes encoding \u03b13, \u03b14 or \u03b15 chains of collagen IV<\/jats:styled-content> (COL4A3<\/jats:styled-content>\/COL4A4<\/jats:styled-content>\/COL4A5<\/jats:styled-content><\/jats:italic>), resulting in hematuria, chronic renal failure (CRF<\/jats:styled-content>), sensorineural hearing loss (SNHL<\/jats:styled-content>) and ocular abnormalities. Mutations in the X\u2010linked COL4A5<\/jats:styled-content><\/jats:italic> gene have been identified in 85% of the families (XLAS<\/jats:styled-content>). In this study, 22 of 60 probands (37%) of unrelated Portuguese families, with clinical diagnosis of AS<\/jats:styled-content> and no evidence of autosomal inheritance, had pathogenic COL4A5<\/jats:styled-content><\/jats:italic> mutations detected by Sanger sequencing and\/or multiplex\u2010ligation probe amplification, of which 12 (57%) are novel. Males had more severe and earlier renal and extrarenal complications, but microscopic hematuria was a constant finding irrespective of gender. Nonsense and splice site mutations, as well as small and large deletions, were associated with younger age of onset of SNHL<\/jats:styled-content> in males, and with higher risk of CRF<\/jats:styled-content> and SNHL<\/jats:styled-content> in females. Pathogenic COL4A3<\/jats:styled-content><\/jats:italic> or COL4A4<\/jats:styled-content><\/jats:italic> mutations were subsequently identified in more than half of the families without a pathogenic mutation in COL4A5<\/jats:styled-content><\/jats:italic>. The lower than expected prevalence of XLAS<\/jats:styled-content> in Portuguese families warrants the use of next\u2010generation sequencing for simultaneous COL4A3<\/jats:styled-content>\/COL4A4<\/jats:styled-content>\/COL4A5<\/jats:styled-content><\/jats:italic> analysis, as first\u2010tier approach to the genetic diagnosis of collagen type IV<\/jats:styled-content>\u2010related nephropathies.<\/jats:p>","DOI":"10.1111\/cge.12522","type":"journal-article","created":{"date-parts":[[2014,10,13]],"date-time":"2014-10-13T06:59:57Z","timestamp":1413183597000},"page":"462-467","source":"Crossref","is-referenced-by-count":8,"title":["Collagen type IV<\/scp>\u2010related nephropathies in Portugal: pathogenic COL4A5<\/scp><\/i> mutations and clinical characterization of 22 families"],"prefix":"10.1111","volume":"88","author":[{"given":"M.J.","family":"Nabais S\u00e1","sequence":"first","affiliation":[{"name":"Department of Genetics Faculty of Medicine Porto Portugal"},{"name":"Unit of 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Research and Development of Nephrology (FCT\u2010725), Faculty of Medicine University of Porto Porto Portugal"},{"name":"Dialysis Clinic of Santo Tirso Uninefro Santo Tirso Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Freitas","sequence":"additional","affiliation":[{"name":"Department of Nephrology Centro Hospitalar e Universit\u00e1rio de Coimbra Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.C.","family":"Sousa","sequence":"additional","affiliation":[{"name":"Department of Nephrology Hospital de S\u00e3o Teot\u00f3nio Viseu Portugal"},{"name":"Dialysis Clinic of Guarda NephroCare\u2010Portugal Guarda Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.C.","family":"Henriques","sequence":"additional","affiliation":[{"name":"Dialysis Clinic of Braga NephroCare\u2010Portugal Braga 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