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Most TS cases are caused by a de novo missense mutation in the\n                    <jats:italic>CACNA1C<\/jats:italic>\n                    gene that encodes the pore-forming subunit of the voltage-gated L-type calcium channel Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2. Patients show highly variable clinical presentations and survival, which may be impacted by acute episodes of hypoglycemia and respiratory dysfunction. In addition, fever, known to activate Ca\n                    <jats:sub>V<\/jats:sub>\n                    1.2 channels, may exacerbate TS, yet its impact is poorly understood. We generated a zebrafish model carrying the homologous\n                    <jats:italic>cacna1c<\/jats:italic>\n                    mutation. These fish exhibited arrhythmias, increased susceptibility to pentylenetetrazole-induced seizures, microcephaly, cerebellar hypotrophy and abnormal GABAergic neuron development. Transcriptomic analysis revealed dysregulated expression of neuropeptides including\n                    <jats:italic>bdnf<\/jats:italic>\n                    and\n                    <jats:italic>vgf<\/jats:italic>\n                    . Notably, elevated water temperature elicited arrhythmia and seizure-like behavior even in overtly normal heterozygotes, implicating fever as a modifiable risk. This model provides a platform for dissecting TS pathophysiology and identifying strategies to mitigate fever-related risk.\n                  <\/jats:p>","DOI":"10.1038\/s42003-026-10657-3","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T12:14:13Z","timestamp":1783599253000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elevated body temperature exacerbates arrhythmia and seizure-like activity in a zebrafish model of Timothy syndrome"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2311-4142","authenticated-orcid":false,"given":"Svetlana A.","family":"Semenova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir M.","family":"Sams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepthi","family":"Nammi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Menold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennady","family":"Margolin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9860-7738","authenticated-orcid":false,"given":"Jennifer L.","family":"Sinclair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katelyn A.","family":"Robertson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6410-9337","authenticated-orcid":false,"given":"Kerry","family":"Larkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney","family":"Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Golden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Feldman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1966-7801","authenticated-orcid":false,"given":"Harold A.","family":"Burgess","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"10657_CR1","doi-asserted-by":"publisher","first-page":"668546","DOI":"10.3389\/fped.2021.668546","volume":"9","author":"R Bauer","year":"2021","unstructured":"Bauer, R., Timothy, K. 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