{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:45:50Z","timestamp":1791978350202,"version":"4.4.0"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T00:00:00Z","timestamp":1642118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p>We investigated the existence and potential pathogenicity of a <jats:italic>SLC9A6<\/jats:italic> splicing variant in a Chinese boy with Christianson Syndrome (CS), which was reported for the first time in China. Trio whole-exome sequencing (WES) was performed in the proband and his parents. Multiple computer prediction tools were used to evaluate the pathogenicity of the variant, and reverse transcription-polymerase chain reaction (RT-PCR) analysis and cDNA sequencing were performed to verify the RNA splicing results. The patient presented with characteristic features of CS: global developmental delay, seizures, absent speech, truncal ataxia, microcephaly, ophthalmoplegia, smiling face and hyperkinesis with electrical status epilepticus during sleep (ESES) detected in an electroencephalogram (EEG). A <jats:italic>SLC9A6<\/jats:italic> splicing variant was identified by WES and complete skipping of exon 10 was confirmed by RT-PCR. This resulted in altered gene function and was predicted to be pathogenic. ESES observed early in the disease course is considered to be a significant feature of CS with the <jats:italic>SLC9A6<\/jats:italic> variant. Combined genetic analysis at both the DNA and RNA levels is necessary to confirm the pathogenicity of this variant and its role in the clinical diagnosis of CS.<\/jats:p>","DOI":"10.3389\/fneur.2021.796283","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T04:40:10Z","timestamp":1642135210000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Case Report: Novel SLC9A6 Splicing Variant in a Chinese Boy With Christianson Syndrome With Electrical Status Epilepticus During Sleep"],"prefix":"10.3389","volume":"12","author":[{"given":"Xiaorui","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixu","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"104490","DOI":"10.1016\/j.nbd.2019.104490","article-title":"A Christianson syndrome-linked deletion mutation (\u0394287ES288) in SLC9A6 impairs hippocampal neuronal plasticity","volume":"130","author":"Gao","year":"2019","journal-title":"Neurobiol Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1002\/ajmg.c.31400","article-title":"Genetic disorders associated with postnatal microcephaly","author":"Seltzer","year":"2014","journal-title":"Am J Med Genet C Semin Med Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"100349","DOI":"10.1016\/j.ebr.2019.100349","article-title":"Epilepsy in Christianson syndrome: Two cases of Lennox-Gastaut syndrome and a review of literature","volume":"13","author":"Ikeda","year":"2020","journal-title":"Epilepsy Behav Rep."},{"key":"B4","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1002\/ajmg.b.31221","article-title":"A loss-of-function mutation in the SLC9A6 gene causes X-linked mental retardation resembling Angelman syndrome","author":"Takahashi","year":"2011","journal-title":"Am J Med Genet B Neuropsychiatr Genet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/ng.806","article-title":"A framework for variation discovery and genotyping using next-generation DNA sequencing data","volume":"43","author":"DePristo","year":"2011","journal-title":"Nat Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"3369","DOI":"10.1093\/brain\/awr250","article-title":"X-linked Angelman-like syndrome caused by Slc9a6 knockout in mice exhibits evidence of endosomal-lysosomal dysfunction","volume":"134","author":"Str\u00f8mme","year":"2011","journal-title":"Brain."},{"key":"B8","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.neuron.2013.07.043","article-title":"Christianson syndrome protein NHE6 modulates TrkB endosomal signaling required for neuronal circuit development","volume":"80","author":"Ouyang","year":"2013","journal-title":"Neuron."},{"key":"B9","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1111\/j.1399-0004.2012.01948.x","article-title":"Novel SLC9A6 mutations in two families with Christianson syndrome","volume":"83","author":"Riess","year":"2013","journal-title":"Clin Genet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1016\/j.eplepsyres.2014.02.009","article-title":"A novel mutation in the endosomal Na+\/H+ exchanger NHE6 (SLC9A6) causes Christianson syndrome with electrical status epilepticus during slow-wave sleep (ESES)","volume":"108","author":"Zanni","year":"2014","journal-title":"Epilepsy Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/s41439-019-0046-x","article-title":"A novel splicing mutation in SLC9A6 in a boy with Christianson syndrome","volume":"6","author":"Ieda","year":"2019","journal-title":"Hum Genome Var."},{"key":"B12","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.nbd.2018.10.002","article-title":"A potential gain-of-function variant of SLC9A6 leads to endosomal alkalinization and neuronal atrophy associated with Christianson Syndrome","volume":"121","author":"Ilie","year":"2019","journal-title":"Neurobiol Dis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"7075","DOI":"10.1074\/jbc.RA120.012614","article-title":"Assorted dysfunctions of endosomal alkali cation\/proton exchanger SLC9A6 variants linked to Christianson syndrome","volume":"295","author":"Ilie","year":"2020","journal-title":"J Biol Chem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1002\/ana.24225","article-title":"Genetic and phenotypic diversity of NHE6 mutations in Christianson syndrome","volume":"76","author":"Pescosolido","year":"2014","journal-title":"Ann Neurol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1016\/j.ejpn.2018.07.004","article-title":"Electrical status epilepticus in sleep, a constitutive feature of Christianson syndrome?","volume":"22","author":"Mathieu","year":"2018","journal-title":"Eur J Paediatr Neurol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1007\/s00439-016-1675-5","article-title":"The expanding phenotypic spectrum of female SLC9A6 mutation carriers: a case series and review of the literature","volume":"135","author":"Sinajon","year":"2016","journal-title":"Hum Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2103","DOI":"10.1002\/ajmg.a.37765","article-title":"A new family with an SLC9A6 mutation expanding the phenotypic spectrum of Christianson syndrome","volume":"170","author":"Masurel-Paulet","year":"2016","journal-title":"Am J Med Genet A."},{"key":"B18","doi-asserted-by":"publisher","first-page":"607965","DOI":"10.3389\/fgene.2021.607965","article-title":"Genetic etiologies in developmental and\/or epileptic encephalopathy with electrical status epilepticus during sleep: Cohort Study","volume":"12","author":"Gong","year":"2021","journal-title":"Front Genet."},{"key":"B19","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.pediatrneurol.2015.07.007","article-title":"Successful treatment of electrographic status epilepticus of sleep with felbamate in a patient with SLC9A6 mutation","volume":"53","author":"Coorg","year":"2015","journal-title":"Pediatr Neurol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1126\/scitranslmed.aaw0682","article-title":"Human neurons from Christianson syndrome iPSCs reveal mutation-specific responses to rescue strategies","volume":"13","author":"Lizarraga","year":"2021","journal-title":"Sci Transl Med."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.796283\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T04:40:13Z","timestamp":1642135213000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.796283\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,14]]},"references-count":20,"alternative-id":["10.3389\/fneur.2021.796283"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2021.796283","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,14]]},"article-number":"796283"}}