{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T16:02:13Z","timestamp":1783612933036,"version":"3.55.0"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T00:00:00Z","timestamp":1723161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Alport syndrome (AS) is a common cause of end-stage renal disease (ESRD) with various clinical symptoms and incomplete manifestation. Patients with AS and other renal disorders are often misdiagnosed. This study reported three X-linked dominant Alport syndrome (XLAS) pedigrees with nephrotic syndrome (NS) as the predominant phenotype and analyzed <jats:italic>COL4A5<\/jats:italic> gene alterations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Three Han Chinese XLAS pedigrees were recruited, and clinical phenotypes were obtained. The pre-certified individuals\u2019 peripheral blood DNA was taken, and whole-genome next-generation sequencing (NGS) was performed for candidate genes and mutation screening, followed by NGS or Sanger sequencing of suspected mutant types in participating family members.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both probands A and B were diagnosed with NS through biochemical tests, and X-linked Alport syndrome-associated renal injury was diagnosed by renal biopsy. The biopsy revealed focal foamy cells in the renal interstitium, tearing and delamination changes in the glomerular basement membrane, and negative \u03b13 and \u03b15 chains of type IV collagen. Proband C, who was earlier diagnosed with NS, has now advanced to ESRD, along with his mother and proband A\u2019s mother. Genetic sequencing of all three pedigrees identified three mutations, namely, c.5020C&amp;gt;T, c.4435_4445del, and c.1584_1587+6del in the X-linked dominant gene <jats:italic>COL4A5<\/jats:italic> (NM_000495.5). These mutations lead to the production of shortened proteins, potentially impacting the function of COL4A5 and causing pathogenic effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The novel c.4435_4445del and c.1584_1587+6del mutations not only enrich the spectrum of mutations in the <jats:italic>COL4A5<\/jats:italic> gene but also indicate that carriers of both mutation sites and those with mutation c.5020C&amp;gt;T may present NS as their primary clinical manifestation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fgene.2024.1419154","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T04:43:14Z","timestamp":1723178594000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Analyzing three pedigrees in X-linked Alport syndrome with the presentation of nephrotic syndrome"],"prefix":"10.3389","volume":"15","author":[{"given":"Jian-Hui","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan-Dan","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Ping","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Sheng","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ling","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie-Wei","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.3760\/cma.j.cn112137-20230203-00161","volume":"103","year":"2023","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"B2","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1093\/ndt\/gfz028","article-title":"Personalized medicine in chronic kidney disease by detection of monogenic mutations","volume":"35","author":"Connaughton","year":"2020","journal-title":"Nephrol. 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