{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:44:20Z","timestamp":1780472660743,"version":"3.54.1"},"reference-count":17,"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":"Regional Development Fund"},{"name":"Portuguese Foundation for Science and Technology (FCT)"},{"name":"Portuguese Society of Nephrology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2015,11]]},"abstract":"Pathogenic mutations in genes COL4A3<\/jats:styled-content>\/COL4A4<\/jats:styled-content><\/jats:italic> are responsible for autosomal Alport syndrome (AS<\/jats:styled-content>) and thin basement membrane nephropathy (TBMN<\/jats:styled-content>). We used Sanger sequencing to analyze all exons and splice site regions of COL4A3<\/jats:styled-content><\/jats:italic>\/COL4A4<\/jats:styled-content><\/jats:italic>, in 40 unrelated Portuguese probands with clinical suspicion of AS<\/jats:styled-content>\/TBMN<\/jats:styled-content>. To assess genotype\u2013phenotype correlations, we compared clinically relevant phenotypes\/outcomes between homozygous\/compound heterozygous and apparently heterozygous patients. Seventeen novel and four reportedly pathogenic COL4A3<\/jats:styled-content>\/COL4A4<\/jats:styled-content><\/jats:italic> mutations were identified in 62.5% (25\/40) of the probands. Regardless of the mutated gene, all patients with ARAS<\/jats:styled-content> manifested chronic renal failure (CRF<\/jats:styled-content>) and hearing loss, whereas a minority of the apparently heterozygous patients had CRF<\/jats:styled-content> or extrarenal symptoms. CRF<\/jats:styled-content> was diagnosed at a significantly younger age in patients with ARAS<\/jats:styled-content>. In our families, the occurrence of COL4A3<\/jats:styled-content><\/jats:italic>\/COL4A4<\/jats:styled-content><\/jats:italic> mutations was higher, while the prevalence of XLAS<\/jats:styled-content> was lower than expected. Overall, a pathogenic COL4A3<\/jats:styled-content><\/jats:italic>\/COL4A4<\/jats:styled-content><\/jats:italic>\/COL4A5<\/jats:styled-content><\/jats:italic> mutation was identified in >50% of patients with fewer than three of the standard diagnostic criteria of AS<\/jats:styled-content>. With such a population background, simultaneous next\u2010generation sequencing of all three genes may be recommended as the most expedite approach to diagnose collagen IV<\/jats:styled-content>\u2010related glomerular basement membrane nephropathies.<\/jats:p>","DOI":"10.1111\/cge.12521","type":"journal-article","created":{"date-parts":[[2014,10,13]],"date-time":"2014-10-13T06:58:54Z","timestamp":1413183534000},"page":"456-461","source":"Crossref","is-referenced-by-count":21,"title":["Collagen type IV<\/scp>\u2010related nephropathies in Portugal: pathogenic COL4A3<\/scp><\/i> and COL4A4<\/scp><\/i> mutations and clinical characterization of 25 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 Research and Development of Nephrology (FCT\u2010725), Faculty of Medicine University of Porto Porto 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