{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T08:12:03Z","timestamp":1783930323052,"version":"3.55.0"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T00:00:00Z","timestamp":1554768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T00:00:00Z","timestamp":1554768000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Alport syndrome (AS) is an inherited progressive renal disease caused by mutations in\n                      <jats:italic>COL4A3<\/jats:italic>\n                      ,\n                      <jats:italic>COL4A4<\/jats:italic>\n                      , and\n                      <jats:italic>COL4A5<\/jats:italic>\n                      genes. The large sizes of these genes and the absence of mutation hot spots have complicated mutational analysis by routine PCR\u2010based approaches. In recent years, the development of next\u2010generation sequencing (NGS) has made possible the time\u2010 and cost\u2010effective and accurate analysis of the three genes in a single step.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Here, we analyze\n                      <jats:italic>COL4A3<\/jats:italic>\n                      ,\n                      <jats:italic>COL4A4<\/jats:italic>\n                      , and\n                      <jats:italic>COL4A5<\/jats:italic>\n                      simultaneously in 29 AS patients using NGS. Candidate mutations were validated by classic Sanger sequencing and Real\u2010time PCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty two new mutations and 10 known mutations were detected. Of those novel mutations, 18, 3, and 1 mutations were detected in\n                      <jats:italic>COL4A5<\/jats:italic>\n                      ,\n                      <jats:italic>COL4A4<\/jats:italic>\n                      , and\n                      <jats:italic>COL4A3<\/jats:italic>\n                      , respectively. Twenty six patients showed\n                      <jats:italic>X<\/jats:italic>\n                      \u2010linked inheritance, one showed autosomal recessive inheritance and two showed digenic inheritance (DI).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      A comparison of the clinical manifestations caused by different types of mutations in\n                      <jats:italic>COL4A5<\/jats:italic>\n                      suggested that large fragment mutations are relatively more severe than the other missense mutations and AS by some mutations may show inter\u2010 and intra\u2010familial phenotypic variability. It is important to consider these transmission patterns in the clinical evaluation according to the results of genetic testing, especially for DI. Twenty two new mutations can expand the genotypic spectrum of AS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.653","type":"journal-article","created":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T22:20:06Z","timestamp":1554848406000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Novel mutations of\n                    <i>COL4A3<\/i>\n                    ,\n                    <i>COL4A4<\/i>\n                    , and\n                    <i>COL4A5<\/i>\n                    genes in Chinese patients with Alport Syndrome using next generation sequence technique"],"prefix":"10.1002","volume":"7","author":[{"given":"Xuechao","family":"Zhao","sequence":"first","affiliation":[{"name":"Genetics and Prenatal Diagnosis Center The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Gene Editing of Human Genetic Disease, Erqi District Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Chen","sequence":"additional","affiliation":[{"name":"Genetics and Prenatal Diagnosis Center The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Gene Editing of Human Genetic Disease, Erqi District Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfu","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Nephrology The First Affiliated Hospital of Zhengzhou University, Research Institute of Nephrology, Zhengzhou University Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganye","family":"Zhao","sequence":"additional","affiliation":[{"name":"Genetics and Prenatal Diagnosis Center The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Gene Editing of Human Genetic Disease, Erqi District Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Liu","sequence":"additional","affiliation":[{"name":"Genetics and Prenatal Diagnosis Center The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Gene Editing of Human Genetic Disease, Erqi District Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conghui","family":"Wang","sequence":"additional","affiliation":[{"name":"Genetics and Prenatal Diagnosis Center The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Gene Editing of Human Genetic Disease, Erqi District Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology The First Affiliated Hospital of Zhengzhou University, Research Institute of Nephrology, Zhengzhou University Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5685-8055","authenticated-orcid":false,"given":"Xiangdong","family":"Kong","sequence":"additional","affiliation":[{"name":"Genetics and Prenatal Diagnosis Center The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Gene Editing of Human Genetic Disease, Erqi District Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.164"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2349482"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009070784"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380050303"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004670050025"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12919"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12258"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/17.7.1218"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneph0671"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.00200110"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra022296"},{"issue":"4","key":"e_1_2_7_13_1","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1681\/ASN.V114649","article-title":"X\u2010linked Alport syndrome: Natural history in 195 families and genotype\u2010 phenotype correlations in males","volume":"11","author":"Jais J. 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