{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:38:23Z","timestamp":1792787903197,"version":"4.5.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T00:00:00Z","timestamp":1720396800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T00:00:00Z","timestamp":1720396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Key S&T Special Projects","award":["2021YFC100530, 2022YFC2703303"],"award-info":[{"award-number":["2021YFC100530, 2022YFC2703303"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32170617, 31970558"],"award-info":[{"award-number":["32170617, 31970558"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100014857","name":"National Natural Science Foundation of China-Guangdong Joint Fund","doi-asserted-by":"publisher","award":["2022A1515012621"],"award-info":[{"award-number":["2022A1515012621"]}],"id":[{"id":"10.13039\/501100014857","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Planning Project of Shenzhen Municipality","award":["JCYJ20220531094201002"],"award-info":[{"award-number":["JCYJ20220531094201002"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genomics"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alport syndrome (AS) is an inherited nephropathy caused by mutations in the type IV collagen genes. It is clinically characterized by damage to the eyes, ears and kidneys. Diagnosis of AS is hampered by its atypical clinical picture, particularly when the typical features, include persistent hematuria and microscopic changes in the glomerular basement membrane (GBM), are the only clinical manifestations in the patient.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We screened 10 families with suspected AS using whole exome sequencing (WES) and analyzed the harmfulness, conservation, and protein structure changes of mutated genes. In further, we performed in vitro functional analysis of two missense mutations in the\n                      <jats:italic>COL4A5<\/jats:italic>\n                      gene (c.2359G\u2009&gt;\u2009C, p.G787R and c.2605G\u2009&gt;\u2009A, p.G869R).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified 11 pathogenic variants in the type IV collagen genes (\n                      <jats:italic>COL4A3<\/jats:italic>\n                      ,\n                      <jats:italic>COL4A4<\/jats:italic>\n                      and\n                      <jats:italic>COL4A5<\/jats:italic>\n                      ). These pathogenic variants include eight missense mutations, two nonsense mutations and one frameshift mutation. Notably, Family 2 had digenic mutations in the\n                      <jats:italic>COL4A3<\/jats:italic>\n                      (p.G1170A) and\n                      <jats:italic>UMOD<\/jats:italic>\n                      genes (p.M229K). Family 3 had a digenic missense mutation (p.G997E) in\n                      <jats:italic>COL4A3<\/jats:italic>\n                      and a frameshift mutation (p.P502L fs*151) in\n                      <jats:italic>COL4A4<\/jats:italic>\n                      . To our knowledge, four of the 11 mutations are novel mutations. In addition, we found that\n                      <jats:italic>COL4A5<\/jats:italic>\n                      mutation relation mRNA levels were significantly decreased in HEK 293\u00a0T cell compared to control, while the cellular localization remained the same.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our research expands the spectrum of\n                      <jats:italic>COL4A3<\/jats:italic>\n                      -5 pathogenic variants, which is helpful for clinical and scientific research.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12920-024-01953-0","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T01:01:51Z","timestamp":1720400511000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Four novel mutations identified in the COL4A3, COL4A4 and COL4A5 genes in 10 families with Alport syndrome"],"prefix":"10.1186","volume":"17","author":[{"given":"Duocai","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meize","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minchun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbo","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,8]]},"reference":[{"issue":"4960","key":"1953_CR1","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1126\/science.2349482","volume":"248","author":"DF Barker","year":"1990","unstructured":"Barker DF, et al. 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