{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:34:12Z","timestamp":1789450452344,"version":"build-2803163510"},"reference-count":34,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T00:00:00Z","timestamp":1738972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Culture, Sports, Science, and Technology of Japan","award":["22K07547"],"award-info":[{"award-number":["22K07547"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Familial hemiplegic migraine (FHM) is characterized by repeated episodes of reversible localized neurological deficits, in addition to headache. The aura of HM includes visual, sensory, motor, and verbal symptoms. Hemiplegic migraine (HM) is classified into non-familial sporadic HM (SHM) and familial HM (FHM). Here, we analyzed the clinical symptoms and their relevance in four Japanese patients considered to have SCN1A mutations as a cause. Sequencing of SCN1A was performed using a whole exome sequence method in 48 blood samples from clinically suspected patients with FHM. Subsequently, algorithm analysis, allele frequency determination, and three-dimensional structure analysis of the recognized variants were performed, and the recognized variants were evaluated. We found five heterozygous missense mutations (p.A23E, p.V250L, p.T398M, p.R1575C, p.L1660I) in SCN1A, three of which had not been reported. These five mutations may also affect the structure of the protein products, as assessed using a three-dimensional structural analysis. In all cases, the clinical symptoms included visual, sensory, motor, and verbal symptoms, which are forms of aura. Similarities were detected, such as the appearance of symptoms at a young age and other symptoms, such as hemiplegia after a headache attack. We report five missense mutations in SCN1A of Japanese cases.<\/jats:p>","DOI":"10.3390\/ijms26041426","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T04:44:03Z","timestamp":1739162643000},"page":"1426","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Expanding the Genetic and Clinical Spectrum of SCN1A-Related Hemiplegic Migraine: Analysis of Mutations in Japanese"],"prefix":"10.3390","volume":"26","author":[{"given":"Daisuke","family":"Danno","sequence":"first","affiliation":[{"name":"Headache Center, Department of Neurology, Tominaga Hospital Japan, Osaka 556-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruka","family":"Tada","sequence":"additional","affiliation":[{"name":"Department of Life Science, Faculty of Science and Engineering, Kindai University, Osaka 577-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itsuki","family":"Oda","sequence":"additional","affiliation":[{"name":"Department of Life Science, Faculty of Science and Engineering, Kindai University, Osaka 577-8502, Japan"},{"name":"Department of Clinical Genetics, Kindai University Hospital Japan, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihito","family":"Kawashita","sequence":"additional","affiliation":[{"name":"Department of Life Science, Faculty of Science and Engineering, Kindai University, Osaka 577-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makito","family":"Hirano","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Kindai University, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigekazu","family":"Kitamura","sequence":"additional","affiliation":[{"name":"Department of Neurology, Konan Medical Center, Kobe 658-0064, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoji","family":"Kikui","sequence":"additional","affiliation":[{"name":"Headache Center, Department of Neurology, Tominaga Hospital Japan, Osaka 556-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3464-0754","authenticated-orcid":false,"given":"Makoto","family":"Samukawa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Kindai University, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7168-0623","authenticated-orcid":false,"given":"Keisuke","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Kindai University, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Mitsui","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Kindai University, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1037-3129","authenticated-orcid":false,"given":"Yoshitaka","family":"Nagai","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine, Kindai University, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2678-6956","authenticated-orcid":false,"given":"Takao","family":"Takeshima","sequence":"additional","affiliation":[{"name":"Headache Center, Department of Neurology, Tominaga Hospital Japan, Osaka 556-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumasa","family":"Saigoh","sequence":"additional","affiliation":[{"name":"Department of Life Science, Faculty of Science and Engineering, Kindai University, Osaka 577-8502, Japan"},{"name":"Department of Clinical Genetics, Kindai University Hospital Japan, Osaka 589-8511, Japan"},{"name":"Department of Neurology, Faculty of Medicine, Kindai University, Osaka 589-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1046\/j.1468-2982.1997.1701015.x","article-title":"Prevalence of migraine in Japan: A nationwide survey","volume":"17","author":"Sakai","year":"1997","journal-title":"Cephalalgia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1055\/s-0030-1249220","article-title":"The epidemiology of primary headache disorders","volume":"30","author":"Robbins","year":"2010","journal-title":"Semin. 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