{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:56:52Z","timestamp":1780505812716,"version":"3.54.1"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T00:00:00Z","timestamp":1630627200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T00:00:00Z","timestamp":1630627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Science and Technology Development Fund of Nanjing Medical University","award":["NMUB2020091"],"award-info":[{"award-number":["NMUB2020091"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pediatr"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The Raynaud-Claes type of X-linked syndromic mental retardation (MRXSRC) is a very rare condition, by intellectual disability ranged from borderline to profound, impaired language development, brain abnormalities, facial dysmorphisms and seizures. MRXSRC is caused by variants in <jats:italic>CLCN4<\/jats:italic> which encodes the 2Cl<jats:sup>\u2212<\/jats:sup>\/H<jats:sup>+<\/jats:sup> exchanger ClC-4 prominently expressed in brain.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>We present a 3-year-old Chinese girl with intellectual disability, dysmorphic features, brain abnormalities, significant language impairment and autistic features. Brain magnetic resonance imaging (MRI) showed a thin corpus callosum, a mega cisterna magna and ventriculomegaly. Whole exome sequencing (WES) was performed to detect the molecular basis of the disease. It was confirmed that this girl carried a novel heterozygous missense variant (c.1343C\u2009&gt;\u2009T, p.Ala448Val) of <jats:italic>CLCN4<\/jats:italic> gene, inherited from her mother. This variant has not been registered in public databases and was predicted to be pathogenic by multiple in silico prediction tools.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our investigation expands the phenotype spectrum for <jats:italic>CLCN4<\/jats:italic> variants with syndromic X-linked intellectual disability, which help to improve the understanding of <jats:italic>CLCN4<\/jats:italic>-related intellectual disability and will help in genetic counselling for this family.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12887-021-02860-4","type":"journal-article","created":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T08:31:45Z","timestamp":1630657905000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Novel CLCN4 variant associated with syndromic X-linked intellectual disability in a Chinese girl: a case report"],"prefix":"10.1186","volume":"21","author":[{"given":"Xin","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fen","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5755-4037","authenticated-orcid":false,"given":"Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senjie","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,3]]},"reference":[{"issue":"1","key":"2860_CR1","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/mp.2014.193","volume":"21","author":"H Hu","year":"2016","unstructured":"Hu H, Haas SA, Chelly J, Van Esch H, Raynaud M, de Brouwer AP, et al. X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes. Mol Psychiatry. 2016;21(1):133\u201348.","journal-title":"Mol Psychiatry"},{"issue":"2","key":"2860_CR2","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1038\/mp.2016.135","volume":"23","author":"EE Palmer","year":"2018","unstructured":"Palmer EE, Stuhlmann T, Weinert S, Haan E, Van Esch H, Holvoet M, et al. De novo and inherited mutations in the X-linked gene CLCN4 are associated with syndromic intellectual disability and behavior and seizure disorders in males and females. Mol Psychiatry. 2018;23(2):222\u201330.","journal-title":"Mol Psychiatry"},{"issue":"7","key":"2860_CR3","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1111\/epi.12201","volume":"54","author":"KR Veeramah","year":"2013","unstructured":"Veeramah KR, Johnstone L, Karafet TM, Wolf D, Sprissler R, Salogiannis J, et al. 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Written informed consent was obtained from the parents.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"A written informed consent was obtained from the patient\u2019s parents for publication of this case report and any accompanying images. All authors have viewed and agreed to the submission.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"384"}}