{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:33:09Z","timestamp":1793316789824,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T00:00:00Z","timestamp":1614643200000},"content-version":"vor","delay-in-days":60,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["2020A1515011287"],"award-info":[{"award-number":["2020A1515011287"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>Alport syndrome (AS) is an inherited kidney disease caused by defects in type IV collagen, which is characterized by hematuria, progressive nephritis or end\u2010stage renal disease (ESRD), hearing loss, and occasionally ocular lesions. Approximately 80% of AS cases are caused by X\u2010linked mutations in the <jats:italic>COL4A5<\/jats:italic> gene. This study explored novel deletion and missense mutations in <jats:italic>COL4A5<\/jats:italic> responsible for renal disorder in two Han Chinese families. In pedigree 1, the five male patients all had ESRD at a young age, while the affected female members only presented with microscopic hematuria. Whole exome sequencing and Sanger sequencing identified a novel frameshift deletion mutation (c.422_428del, p.Leu142Valfs\u221711) in exon 7 of <jats:italic>COL4A5<\/jats:italic>. In pedigree 2, the 16\u2010year\u2010old male proband had elevated serum creatinine (309\u2009<jats:italic>\u03bc<\/jats:italic>mol\/L) without extrarenal manifestations, while his mother only manifested with hematuria. A missense mutation (c.476G&gt;T, p.Gly159Val) was found in exon 9 of the <jats:italic>COL4A5<\/jats:italic> gene. Neither of these mutations was present in the Exome Variant Server of the NHLBI\u2010ESP database, nor was it found in the ExAC or 1000 Genomes databases. Through the literature review, it was found that male Chinese patients with X\u2010linked AS carried <jats:italic>COL4A5<\/jats:italic> deletion or missense mutations had a more severe phenotype than female patients, particularly in proteinuria and impaired renal function. Compared to male patients with missense mutations, patients in whom deletion mutations were found were more likely to progress to ESRD (15.4% vs. 36.0%, <jats:italic>P<\/jats:italic> = 0.041). This study identified two novel <jats:italic>COL4A5<\/jats:italic> mutations in Chinese families with X\u2010linked AS, expanded the mutational spectrum of the <jats:italic>COL4A5<\/jats:italic> gene, and presented findings that are significant for the screening and genetic diagnosis of AS.<\/jats:p>","DOI":"10.1155\/2021\/6664973","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T01:35:22Z","timestamp":1614735322000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Novel Mutations of <i>COL4A5<\/i> Identified in Chinese Families with X\u2010Linked Alport Syndrome and Literature Review"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7660-2417","authenticated-orcid":false,"given":"Wen-yu","family":"Gong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan-na","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang-hong","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7621-9258","authenticated-orcid":false,"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,2]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra022296"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2016.08.005"},{"key":"e_1_2_9_3_2","first-page":"916","article-title":"Advances and unmet needs in genetic, basic and clinical science in Alport syndrome: report from the 2015 International Workshop on Alport Syndrome","volume":"32","author":"Gross O.","year":"2017","journal-title":"Nephrology, Dialysis, Transplantation"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-018-1629-4"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013080912"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V114649"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009070784"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-011-1836-7"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.2174\/1566524019666190906144214"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-014-3227-1"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfh099"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-018-9545-3"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-019-1462-3"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfr184"},{"key":"e_1_2_9_17_2","doi-asserted-by":"crossref","DOI":"10.1002\/mgg3.741","article-title":"Genotype-phenotype correlation and prognostic impact in Chinese patients with Alport syndrome","volume":"7","author":"Shang S.","year":"2019","journal-title":"Molecular genetics & genomic medicine"},{"key":"e_1_2_9_18_2","article-title":"Novel mutations in COL4A3, COL4A4, and COL4A5 in Chinese patients with Alport syndrome","volume":"12","author":"Liu J. 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