{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:02:15Z","timestamp":1753869735283,"version":"3.41.2"},"reference-count":31,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,7,18]],"date-time":"2019-07-18T00:00:00Z","timestamp":1563408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010010","name":"Shanxi Province Science Foundation for Youths","doi-asserted-by":"publisher","award":["201701D221152"],"award-info":[{"award-number":["201701D221152"]}],"id":[{"id":"10.13039\/501100010010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31700731"],"award-info":[{"award-number":["31700731"]}],"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; Gen Med"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Fabry disease (FD), a rare X\u2010linked \u03b1\u2010galactosidase A (GLA) deficiency, resulting in progressive lysosomal accumulation of globotriaosylceramide in a variety of cell types. More and more disease\u2010causing mutations in GLA have been identified in FD due to the advancement of molecular diagnostic tools. We found a novel mutation in a Chinese family with predominant Fabry's disease nephropathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>All coding regions and exon\u2013intron splice junctions of the <jats:italic>GLA<\/jats:italic> gene were sequenced to find sequence variations. We evaluated the impact on the GLA protein by analysis of the GLA mRNA, by sequential analysis and homology modeling, and by site\u2010directed mutagenesis and in vitro expression studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a novel heterozygous missense mutation c.280T&gt;C in our patient with variable phenotypic presentations of renal involvement. The novel GLA variant results in low expression of GLA mRNAs, impaired or loss of the disulfate bridge structure of wild\u2010type GLA, reduced GLA activity and defected nuclear shape in the GFP\u2010GLA\u2010MT transfected HEK293T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A novel GLA missense mutation, c.280T&gt;C (Cys94Arg), was found in a Chinese family with predominant renal manifestations of FD. Our study reveals the pathogenesis of c.280T&gt;C mutation to FD and provides scientific foundation for accurate diagnosis and precise medical intervention for FD.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.864","type":"journal-article","created":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T01:08:56Z","timestamp":1563498536000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Functional evaluation of a novel <i>GLA<\/i> causative mutation in Fabry disease"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6137-6154","authenticated-orcid":false,"given":"Ping","family":"Li","sequence":"first","affiliation":[{"name":"Institutes of Biomedical Sciences Shanxi University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences Shanxi University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1531-7353","authenticated-orcid":false,"given":"Qiuhong","family":"Xiong","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences Shanxi University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The First Hospital, Shanxi Medical University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"Cui","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology Shanxi University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong\u2010An","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Second Hospital, Shanxi Medical University Bluttransfusion Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology The First Hospital, Shanxi Medical University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Xiao","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences Shanxi University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changxin","family":"Wu","sequence":"additional","affiliation":[{"name":"Institutes of Biomedical Sciences Shanxi University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,7,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s100380170088"},{"key":"e_1_2_7_3_1","first-page":"227","article-title":"Fabry disease: Twenty\u2010two novel mutations in the alpha\u2010galactosidase A gene and genotype\/phenotype correlations in severely and mildly affected hemizygotes and heterozygotes","volume":"48","author":"Ashton\u2010Prolla P.","year":"2000","journal-title":"Journal of Investigative Medicine"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1996)8:1<38::AID-HUMU5>3.0.CO;2-L"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1219"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-138-4-200302180-00014"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2013.09.058"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12613"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-90-481-9033-1"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401671"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.10.1795"},{"key":"e_1_2_7_12_1","first-page":"1186","article-title":"Nature and frequency of mutations in the alpha\u2010galactosidase A gene that cause Fabry disease","volume":"53","author":"Eng C. 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