{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:13:39Z","timestamp":1772118819419,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Metachromatic leukodystrophy (MLD) is a rare inherited lysosomal disorder caused by mutations in\n                      <jats:italic>ARSA<\/jats:italic>\n                      . The biological processes of MLD disease caused by candidate pathogenic mutations in the\n                      <jats:italic>ARSA<\/jats:italic>\n                      gene remain unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used whole\u2010exome sequencing (WES) and Sanger sequencing to identify the pathogenic mutation in a Chinese family. Literature review and protein three\u2010dimensional structure prediction were performed to analyze the potential pathogenesis of the identified mutations. Overexpression cell models of wild\u2010type and mutated\n                      <jats:italic>ARSA<\/jats:italic>\n                      genes were constructed. The accumulated sulfatides and expression profiles in the cell models were detected, and a series of bioinformatics analyses were carried out to compare the biological changes caused by the candidate pathogenic mutations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified an\n                      <jats:italic>ARSA<\/jats:italic>\n                      c.925G&gt;A homozygous mutation from a Chinese late\u2010infantile MLD patient, the first report of this mutation in East Asia. The literature and protein structure analysis indicated that three types of mutations at c.925G (c.925G&gt;A, c.925G&gt;T, c.925G&gt;C) were pathogenic. The overexpression of wild\u2010type or mutated\n                      <jats:italic>ARSA<\/jats:italic>\n                      genes influenced the accumulation of sulfatides. The co\u2010expression modules in the mutated cell models were constructed by genes related to calcium signaling and vesicle transport.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our results identified a pathogenic mutation,\n                      <jats:italic>ARSA<\/jats:italic>\n                      homozygosity c.925G&gt;A, from a Chinese MLD family. The pathogenic mechanism of the\n                      <jats:italic>ARSA<\/jats:italic>\n                      mutation in MLD was identified, which may suggest new approaches to diagnosis and treatment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.1478","type":"journal-article","created":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T01:31:20Z","timestamp":1599010280000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Identification of a missense\n                    <i>ARSA<\/i>\n                    mutation in metachromatic leukodystrophy and its potential pathogenic mechanism"],"prefix":"10.1002","volume":"8","author":[{"given":"Liyuan","family":"Guo","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Mental Health Institute of Psychology Chinese Academy of Sciences  Beijing China"},{"name":"Department of Psychology University of Chinese Academy of Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Neurology Children's Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yidan","family":"Zhang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Mental Health Institute of Psychology Chinese Academy of Sciences  Beijing China"},{"name":"Department of Psychology University of Chinese Academy of Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2512-0223","authenticated-orcid":false,"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Mental Health Institute of Psychology Chinese Academy of Sciences  Beijing China"},{"name":"Department of Psychology University of Chinese Academy of Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/04711\u200b42905.hg072\u200b0s76"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2008.01058.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21093"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22919"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2361068"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/08830\u200b73815\u200b595078"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(20000\u200b1)15:1<7::AID-HUMU4\u200b>3.0.CO;2-N"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s1203\u200b1-013-0006-8"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20851"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2007-8-9-r183"},{"issue":"2","key":"e_1_2_8_12_1","first-page":"171","article-title":"Genetic heterogeneity in metachromatic leukodystrophy","volume":"34","author":"Kihara H.","year":"1982","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1982.tb007\u200b59.x"},{"issue":"2","key":"e_1_2_8_14_1","first-page":"339","article-title":"High residual arylsulfatase A (ARSA) activity in a patient with late\u2010infantile metachromatic leukodystrophy","volume":"53","author":"Kreysing J.","year":"1993","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-559"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi971\u200b4924"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.15252\/\u200bemmm.20150\u200b5850"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journ\u200bal.pbio.0060026"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg509"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1179\/01616\u200b4108X\u200b323762"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.5582\/irdr.2016.01085"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S15467"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.20120\u200b8152"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp939"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijns3\u200b020006"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth\u200b0810-575"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u200b-6736(16)30374\u200b-9"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2014.10.001"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3792"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1478","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.1478","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1478","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T06:58:16Z","timestamp":1708498696000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.1478"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":30,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1002\/mgg3.1478"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.1478","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/822890","asserted-by":"object"}]},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9]]},"assertion":[{"value":"2020-02-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1478"}}