{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T18:05:46Z","timestamp":1785175546899,"version":"3.55.0"},"reference-count":25,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T00:00:00Z","timestamp":1595462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dongguan Social Development Project","award":["201950715007158"],"award-info":[{"award-number":["201950715007158"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pathogenic <jats:italic>KCNA1<\/jats:italic> variants have been linked to episodic ataxia type 1 (EA1), a rare neurological syndrome characterized by continuous myokymia and attacks of generalized ataxia that can be triggered by fever, abrupt movements, emotional stress, and fatigue. Currently, over 40 <jats:italic>KCNA1<\/jats:italic> variants have been identified in individuals with EA1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A male patient displayed partial seizures in addition to EA1 symptoms, often triggered by fever. A sibling presented with typical EA1 symptoms, seizures, and learning difficulties. In addition, the older brother displayed cognitive impairment, developmental delay, and slurred speech, which were absent in his younger sister. Whole\u2010exome sequencing was performed for the patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel <jats:italic>de novo<\/jats:italic> missense variant in <jats:italic>KCNA1<\/jats:italic> (p.Ala261Thr) was identified in the male patient, which is located in a base of the 3rd transmembrane domain (S3). The other novel <jats:italic>KCNA1<\/jats:italic> variant (p.Gly376Ser) was identified in the sibling and was inherited from an unaffected father with low\u2010level mosaicism. The variant was located in the S5\u2013S6 extracellular linker of the voltage sensor domain of the Kv channel. Next, we systematically reviewed the available clinical phenotypes of individuals with EA1 and observed that individuals with <jats:italic>KCNA1<\/jats:italic> variants at the C\u2010terminus were more likely to suffer from seizures and neurodevelopmental disorders than those with variants at the N\u2010terminus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study expands the mutation spectrum of <jats:italic>KCNA1<\/jats:italic> and improves our understanding of the genotype\u2013phenotype correlations of <jats:italic>KCNA1<\/jats:italic>. Definitive genetic diagnosis is beneficial for the genetic counseling and clinical management of individuals with EA1.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1434","type":"journal-article","created":{"date-parts":[[2020,7,24]],"date-time":"2020-07-24T05:23:02Z","timestamp":1595568182000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Two novel <i>KCNA1<\/i> variants identified in two unrelated Chinese families affected by episodic ataxia type 1 and neurodevelopmental disorders"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8510-0419","authenticated-orcid":false,"given":"Haiming","family":"Yuan","sequence":"first","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital Dongguan China"},{"name":"Dongguan Institute of Reproductive and Genetic Research Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihua","family":"Yuan","sequence":"additional","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingming","family":"Wang","sequence":"additional","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital Dongguan China"},{"name":"Dongguan Institute of Reproductive and Genetic Research Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanhua","family":"Ye","sequence":"additional","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital Dongguan China"},{"name":"Dongguan Institute of Reproductive and Genetic Research Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixia","family":"Yao","sequence":"additional","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital Dongguan China"},{"name":"Dongguan Institute of Reproductive and Genetic Research Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanfang","family":"Xu","sequence":"additional","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital Dongguan China"},{"name":"Dongguan Institute of Reproductive and Genetic Research Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1657-0190","authenticated-orcid":false,"given":"Yanhui","family":"Liu","sequence":"additional","affiliation":[{"name":"Dongguan Maternal and Child Health Care Hospital Dongguan China"},{"name":"Dongguan Institute of Reproductive and Genetic Research Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2017.09.003"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00317"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22467"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200010)48:4<647::AID-ANA12>3.0.CO;2-Q"},{"key":"e_1_2_8_6_1","first-page":"1993","volume-title":"GeneReviews\u00ae\u00a0[Internet]","author":"Hasan S. 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