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The clinical characteristics of FMTLE were systematically reviewed, and the pathogenic potential of the identified variant was assessed following the guidelines established by the American College of Medical Genetics and Genomics (ACMG). To explore the underlying pathogenic mechanisms, we utilized bioinformatics tools alongside molecular dynamics simulation methods.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A novel\n                      <jats:italic>CACNA1C<\/jats:italic>\n                      variant (c.5480G\u2009&gt;\u2009A, p.R1827Q) was identified in a large family with FMTLE. Unlike previous reports, the clinical phenotype of this genotype differs from previous reports, being mild, with focal to bilateral tonic\u2013clonic seizures being more common. Bioinformatics analysis and molecular dynamics simulations indicated that this variant induces local structural changes in the protein.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The findings of this study provide new insights into the complex molecular mechanisms underlying\n                      <jats:italic>CACNA1C<\/jats:italic>\n                      variants and their correlations with patient phenotypes. This research is the first to identify\n                      <jats:italic>CACNA1C<\/jats:italic>\n                      as a potentially new pathogenic gene in FMTLE.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s42494-025-00231-5","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:02:47Z","timestamp":1762128167000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expanding clinical phenotype in CACNA1C related disorders: familial mesial temporal lobe epilepsy"],"prefix":"10.1186","volume":"7","author":[{"given":"Chengzhe","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xintong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dingju","family":"Long","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sijing","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinchao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yicong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanzhong","family":"Ni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6790-1258","authenticated-orcid":false,"given":"Ziyi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"issue":"1","key":"231_CR1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.cell.2004.09.011","volume":"119","author":"I Splawski","year":"2004","unstructured":"Splawski I, Timothy KW, Sharpe LM, Decher N, Kumar P, Bloise R, et al. 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