{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:39Z","timestamp":1753869699384,"version":"3.41.2"},"reference-count":18,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T00:00:00Z","timestamp":1707436800000},"content-version":"vor","delay-in-days":8,"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":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare, inherited disorder that causes epilepsy, intellectual disorders, and early onset macrocephaly. <jats:italic>MLC1<\/jats:italic> has been identified as a main pathogenic gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical data such as magnetic resonance imaging (MRI), routine blood tests, and physical examinations were collected from proband. Trio whole\u2010exome sequencing (WES) of the family was performed, and all variants with a minor allele frequency (&lt;0.01) in the exon and canonical splicing sites were selected for further pathogenic evaluation. Candidate variants were validated using Sanger sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we report a new homozygous variant identified in two children from the same family in the <jats:italic>MLC1<\/jats:italic> gene [NM_015166.4: c.838_843delinsATTTTA, (p.Ser280_Phe281delinsIleLeu)]. This variant is classified as variant of uncertain significance (VUS) according to the ACMG guidelines. Further experiments demonstrate that the newly identified variant causes a decrease of MLC1 protein levels when expressed in a heterologous expression system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our case expands on this genetic variation and provides new evidence for the clinical diagnosis of <jats:italic>MLC1<\/jats:italic>\u2010related MLC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2394","type":"journal-article","created":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T05:07:47Z","timestamp":1707541667000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Homozygous variant of MLC1 results in megalencephalic leukoencephalopathy with subcortical cysts"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6967-3698","authenticated-orcid":false,"given":"Jian","family":"Zha","sequence":"first","affiliation":[{"name":"Department of Neurology Jiangxi Provincial Children's Hospital  Nanchang Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology Jiangxi Provincial Children's Hospital  Nanchang Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangfang","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Neurology Jiangxi Provincial Children's Hospital  Nanchang Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology Jiangxi Provincial Children's Hospital  Nanchang Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuozhen","family":"Yang","sequence":"additional","affiliation":[{"name":"Cipher Gene LLC  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu","family":"Wen","sequence":"additional","affiliation":[{"name":"Cipher Gene LLC  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengmeng","family":"Liang","sequence":"additional","affiliation":[{"name":"Cipher Gene LLC  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaping","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology Jiangxi Provincial Children's Hospital  Nanchang Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianmin","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Neurology Jiangxi Provincial Children's Hospital  Nanchang Jiangxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,2,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2020.1699060"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2003-42210"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3343\/alm.2017.37.6.516"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn269"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2017.10.013"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005334"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-019-0540-6"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/319519"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.02.009"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr238"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2013.07.001"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-003-0085-4"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1110s43"},{"volume-title":"Megalencephalic leukoencephalopathy with subcortical cysts","year":"1993","author":"Knaap M. 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