{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:36Z","timestamp":1753869696208,"version":"3.41.2"},"reference-count":33,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,11,7]],"date-time":"2020-11-07T00:00:00Z","timestamp":1604707200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070738","82000079","8200427"],"award-info":[{"award-number":["82070738","82000079","8200427"]}],"id":[{"id":"10.13039\/501100001809","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":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Focal segmental glomerulosclerosis (FSGS), as the frequent primary glomerular diseases in adults, accounts for symptomless proteinuria or nephrotic syndrome with or without renal insufficiency. As the crucial lesion of chronic kidney disease (CKD), accumulating evidence from recent studies show that mutations in Collagen\u2010related genes may be responsible for FSGS. The aim of this study was to identify the genetic lesion of a Chinese family with FSGS and CKD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we recruited a Han\u2010Chinese family with unexplained high serum creatinine, hematuria, and proteinuria. Further renal biopsy and renal pathology indicated the diagnosis of FSGS in the proband. Whole\u2010exome sequencing and Sanger sequencing were employed to explore the pathogenic mutation of this family.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel heterozygous mutation (NM_000092 c.2030G&gt;A, p.G677D) of the <jats:italic>collagen type IV alpha<\/jats:italic>\u2010<jats:italic>4<\/jats:italic> gene (<jats:italic>COL4A4<\/jats:italic>) was detected. Co\u2010segregation analysis revealed that the novel mutation was carried by all the five affected individuals and absent in other healthy members as well as in our 200 local control cohorts. Bioinformatics predication indicated that this novel mutation was pathogenic and may disrupt the structure and function of type IV collagen. Simultaneously, this variant is located in an evolutionarily conserved site of COL4A4 protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Here, we identified a novel mutation of <jats:italic>COL4A4<\/jats:italic> in a family with FSGS and CKD. Our study expanded the variants spectrum of the <jats:italic>COL4A4<\/jats:italic> gene and contributed to the genetic counseling and prenatal genetic diagnosis of the family. In addition, we also recommended the new classification of collagen IV nephropathies, which may be a benefit to the diagnosis, target drug treatment, and management of patients with <jats:italic>COL4A3<\/jats:italic>\/<jats:italic>COL4A4<\/jats:italic> mutations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1545","type":"journal-article","created":{"date-parts":[[2020,11,7]],"date-time":"2020-11-07T16:48:11Z","timestamp":1604767691000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A novel heterozygous variant of the <i>COL4A4<\/i> gene in a Chinese family with hematuria and proteinuria leads to focal segmental glomerulosclerosis and chronic kidney disease"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7431-1838","authenticated-orcid":false,"given":"Liang\u2010Liang","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Nephrology The Third Xiangya Hospital of 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