{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:40:00Z","timestamp":1793317200268,"version":"4.5.0"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,9,25]],"date-time":"2017-09-25T00:00:00Z","timestamp":1506297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2017,11]]},"abstract":"Familial microscopic hematuria (FMH<\/jats:styled-content>) is associated with a genetically heterogeneous group of conditions including the collagen\u2010IV<\/jats:styled-content> nephropathies, the heritable C3<\/jats:styled-content>\/CFHR5<\/jats:styled-content> nephropathy and the glomerulopathy with fibronectin deposits. The clinical course varies widely, ranging from isolated benign familial hematuria to end\u2010stage renal disease (ESRD<\/jats:styled-content>) later in life. We investigated 24 families using next generation sequencing (NGS<\/jats:styled-content>) for 5 genes: COL4A3<\/jats:styled-content>, COL4A4<\/jats:styled-content>, COL4A5<\/jats:styled-content>, CFHR5<\/jats:styled-content><\/jats:italic> and FN1<\/jats:styled-content><\/jats:italic>. In 17 families (71%), we found 15 pathogenic mutations in COL4A3<\/jats:styled-content>\/A4<\/jats:styled-content>\/A5<\/jats:styled-content><\/jats:italic>, 9 of them novel. In 5 families patients inherited classical AS<\/jats:styled-content> with hemizygous X\u2010linked COL4A5<\/jats:styled-content><\/jats:italic> mutations. Even more patients developed later\u2010onset Alport\u2010related nephropathy having inherited heterozygous COL4A3<\/jats:styled-content>\/A4<\/jats:styled-content><\/jats:italic> mutations that cause thin basement membranes. Amongst 62 heterozygous or hemizygous patients, 8 (13%) reached ESRD<\/jats:styled-content>, while 25% of patients with heterozygous COL4A3<\/jats:styled-content>\/A4<\/jats:styled-content><\/jats:italic> mutations, aged >50\u2010years, reached ESRD<\/jats:styled-content>. In conclusion, COL4A<\/jats:styled-content><\/jats:italic> mutations comprise a frequent cause of FMH<\/jats:styled-content>. Heterozygous COL4A3<\/jats:styled-content>\/A4<\/jats:styled-content><\/jats:italic> mutations predispose to renal function impairment, supporting that thin basement membrane nephropathy is not always benign. The molecular diagnosis is essential for differentiating the X\u2010linked from the autosomal recessive and dominant inheritance. Finally, NGS<\/jats:styled-content> technology is established as the gold standard for the diagnosis of FMH<\/jats:styled-content> and associated collagen\u2010IV<\/jats:styled-content> glomerulopathies, frequently averting the need for invasive renal biopsies.<\/jats:p>","DOI":"10.1111\/cge.13077","type":"journal-article","created":{"date-parts":[[2017,6,20]],"date-time":"2017-06-20T16:16:41Z","timestamp":1497975401000},"page":"517-527","source":"Crossref","is-referenced-by-count":39,"title":["Frequent COL4<\/scp><\/i> mutations in familial microhematuria accompanied by later\u2010onset Alport nephropathy due to focal segmental glomerulosclerosis"],"prefix":"10.1111","volume":"92","author":[{"given":"L.","family":"Papazachariou","sequence":"first","affiliation":[{"name":"Molecular Medicine Research Center & Laboratory of Molecular and Medical Genetics, Department of Biological Sciences University of Cyprus Nicosia 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