{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:30Z","timestamp":1753869690950,"version":"3.41.2"},"reference-count":24,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,8,18]],"date-time":"2020-08-18T00:00:00Z","timestamp":1597708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003035","name":"Aase og Ejnar Danielsens Fond","doi-asserted-by":"publisher","award":["10\u2010001761"],"award-info":[{"award-number":["10\u2010001761"]}],"id":[{"id":"10.13039\/501100003035","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":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Alport syndrome is a progressive hereditary kidney disease clinically presenting with haematuria, proteinuria, and early onset end\u2010stage renal disease, and often accompanied by hearing loss and ocular abnormalities. The inheritance is X\u2010linked in the majority of families and caused by sequence variants in the <jats:italic>COL4A5<\/jats:italic> gene encoding the \u03b15\u2010chain of type\u2010IV collagen. The proportion of <jats:italic>de novo COL4A5<\/jats:italic> sequence variants in X\u2010linked Alport syndrome has been reported between 12 and 15% in previous studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In the present study we have systematically investigated the mosaic status of asymptomatic parents of six patients with X\u2010linked Alport syndrome using next\u2010generation sequencing of DNA extracted from different tissues. The deleterious <jats:italic>COL4A5<\/jats:italic> sequence variants in these patients were previously assumed to be <jats:italic>de novo<\/jats:italic>, based on Sanger sequencing of the parents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A low\u2010grade (1%) parental mosaicism was detected in only one out of six families (17%). In addition, in one out of six families (17%), we found that the mutational event probably occurred postzygotic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings highlight the importance of testing for mosaicism in unaffected parents of patients with sequence variants considered to be <jats:italic>de novo<\/jats:italic>, as it may have implications for the recurrence risk and thereby for the genetic counseling of the family.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1452","type":"journal-article","created":{"date-parts":[[2020,8,19]],"date-time":"2020-08-19T02:21:51Z","timestamp":1597803711000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Low frequency of parental mosaicism in <i>de novo COL4A5<\/i> mutations in X\u2010linked Alport syndrome"],"prefix":"10.1002","volume":"8","author":[{"given":"Ole Magnus Bjorgaas","family":"Helle","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Odense University Hospital Odense Denmark"},{"name":"Department of Clinical Research University of Southern Denmark Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Torkild H\u00f8ieggen","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Odense University Hospital Odense Denmark"},{"name":"Department of Clinical Research University of Southern Denmark Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilian Bomme","family":"Ousager","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Odense University Hospital Odense Denmark"},{"name":"Department of Clinical Research University of Southern Denmark Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mads","family":"Thomassen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Odense University Hospital Odense Denmark"},{"name":"Department of Clinical Research University of Southern Denmark Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0087-4739","authenticated-orcid":false,"given":"Jens Michael","family":"Hertz","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Odense University Hospital Odense Denmark"},{"name":"Department of Clinical Research University of Southern Denmark Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,8,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.05.008"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2013.05.045"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3424"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.07.003"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.16.8380"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23364"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.113"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200618"},{"issue":"6","key":"e_1_2_8_10_1","first-page":"1241","article-title":"X\u2010linked inheritance of Alport syndrome: Family P revisited","volume":"35","author":"Hasstedt S. 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