{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T16:25:13Z","timestamp":1759335913932,"version":"3.41.2"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T00:00:00Z","timestamp":1637107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81800787"],"award-info":[{"award-number":["81800787"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Variants in the endosomal solute carrier family 9 member A6 (<jats:italic>SLC9A6<\/jats:italic>)\/(Na<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>)\/H<jats:sup>+<\/jats:sup> exchanger 6 (<jats:italic>NHE6<\/jats:italic>) gene have been linked to epilepsy, speech loss, truncal ataxia, hyperkinesia, and postnatal microcephaly.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In the present study, we evaluated genetic alterations in a 3\u2010year\u2010old Chinese boy displayed features of epilepsy, psychomotor retardation, microcephaly, low body weight, difficulty in feeding, excessive movement, attention loss, ataxia, and cerebellar atrophy and his healthy family using WES method. The identified variant was further confirmed by Sanger sequencing method. Finally, minigene assays were used to verify whether the novel <jats:italic>SLC9A6<\/jats:italic> intronic variant influenced the normal splicing of mRNA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a novel hemizygous splicing variant [NM_001042537.1: c.1463\u20101G&gt;A] in <jats:italic>SLC9A6<\/jats:italic> by trio\u2010based exome sequencing. The minigene expression in vitro confirmed the splicing variant altered a consensus splice acceptor site of <jats:italic>SLC9A6<\/jats:italic> intron 11, resulting in skipping over exon 12.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our finding extends the catalog of pathogenic intronic variants affecting <jats:italic>SLC9A6<\/jats:italic> pre\u2010mRNA splicing and provides a basis for the genetic diagnosis of CS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.24123","type":"journal-article","created":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T07:42:23Z","timestamp":1637221343000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Christianson syndrome: A novel splicing variant of <i>SLC9A6<\/i> causes exon skipping in a Chinese boy and a literature review"],"prefix":"10.1002","volume":"36","author":[{"given":"Xiaoge","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of pediatrics Northwest Women\u2019s and Children\u2019s Hospital Xi\u2019an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of pediatrics Northwest Women\u2019s and Children\u2019s Hospital Xi\u2019an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongli","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of pediatrics Northwest Women\u2019s and Children\u2019s Hospital Xi\u2019an China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Song","sequence":"additional","affiliation":[{"name":"Department of pediatrics Northwest Women\u2019s and Children\u2019s Hospital Xi\u2019an 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