{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:03:17Z","timestamp":1755216197726,"version":"3.43.0"},"reference-count":26,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T00:00:00Z","timestamp":1740268800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>\n<jats:italic>SPTAN1<\/jats:italic> mutations have been reported in association with autosomal dominant early infantile epileptic encephalopathy 5. Individuals present with early\u2010onset seizures and profound intellectual disability. Recent reports suggest a wider spectrum with later\u2010onset seizures and milder developmental delay. Here we describe two patients with loss\u2010of\u2010function variants in <jats:italic>SPTAN1<\/jats:italic>. One patient has ataxia and mild intellectual disability stemming from a <jats:italic>de novo<\/jats:italic> homozygous p.(Gln1448Pro) variant associated with uniparental disomy 9. The second patient, carrying a heterozygous p.(Asn1839del) allele, exhibits more substantial motor issues, developmental delay, and seizures. Ectopically expressed wild\u2010type or variant\u2010containing forms of <jats:italic>sptan1<\/jats:italic> in zebrafish indicate both variants create loss\u2010of\u2010function alleles, with the p.(Gln1448Pro) likely being hypomorphic. This conclusion is supported by reduced protein abundance and localization of Sptan1 variants in axons of developing embryos. Further, unlike wild\u2010type <jats:italic>sptan1<\/jats:italic>, analysis of the p.(Gln1448Pro) variant showed it failed to restore voltage\u2010gated sodium channel localization in <jats:italic>sptan1<\/jats:italic>\u2010null axons. Additional behavioral analyses show supplementation with the amino acid D\u2010aspartate improved motility in <jats:italic>sptan1<\/jats:italic>\u2010null zebrafish, supporting its use for \u03b1\u2010II spectrin\u2010associated motor dysfunction.<\/jats:p>","DOI":"10.1111\/cge.14732","type":"journal-article","created":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T21:38:47Z","timestamp":1740346727000},"page":"231-239","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Loss of Function <i>SPTAN1<\/i> Variants Result in Ataxia and Intellectual Disability"],"prefix":"10.1111","volume":"108","author":[{"given":"Po\u2010Nien","family":"Lu","sequence":"first","affiliation":[{"name":"Greenwood Genetic Center  Greenwood South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chandler","family":"Melton","sequence":"additional","affiliation":[{"name":"University of South Carolina School of 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