{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T20:03:52Z","timestamp":1789243432526,"version":"build-2803163510"},"reference-count":89,"publisher":"SAGE Publications","issue":"17","license":[{"start":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T00:00:00Z","timestamp":1597363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,8,14]],"date-time":"2020-08-14T00:00:00Z","timestamp":1597363200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurotrauma"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:p>\n                    Brain injuries are associated with oxidative stress and a need to restore neuronal homeostasis. Mutations in ion channel genes, in particular\n                    <jats:italic toggle=\"yes\">CACNA1A,<\/jats:italic>\n                    have been implicated in familial hemiplegic migraine (FHM) and in the development of concussion-related symptoms in response to trivial head trauma. The aim of this study was to explore the potential role of variants in other ion channel genes in the development of such responses. We conducted whole exome sequencing (WES) on16 individuals who developed a range of neurological and concussion-related symptoms following minor or trivial head injuries. All individuals were initially tested and shown to be negative for mutations in known FHM genes.\n                  <\/jats:p>\n                  <jats:p>\n                    Variants identified from the WES results were filtered to identify rare variants (minor allele frequency [MAF] &lt;0.01) in genes related to neural processes as well as genes highly expressed in the brain using a combination of\n                    <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                    prediction tools (SIFT, PolyPhen, PredictSNP, Mutation Taster, and Mutation Assessor). Rare (MAF &lt;0.001) or novel heterozygous variants in 7 ion channel genes were identified in 37.5% (6\/16) of the cases (\n                    <jats:italic toggle=\"yes\">CACNA1I, CACNA1C, ATP10A, ATP7B, KCNAB1, KCNJ10,<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">SLC26A4<\/jats:italic>\n                    ), rare variants in neurotransmitter genes were found in 2 cases (\n                    <jats:italic toggle=\"yes\">GABRG1<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">GRIK1<\/jats:italic>\n                    ), and rare variants in 3 ubiquitin-related genes identified in 4 cases (\n                    <jats:italic toggle=\"yes\">SQSTM1<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">TRIM2<\/jats:italic>\n                    , and\n                    <jats:italic toggle=\"yes\">HECTD1<\/jats:italic>\n                    ).\n                  <\/jats:p>\n                  <jats:p>\n                    In this study, the largest proportion of potentially pathogenic variants in individuals with severe responses to minor head trauma were identified in genes previously implicated in migraine and seizure-related autosomal recessive neurological disorders. Together with results implicating variants in the hemiplegic migraine genes,\n                    <jats:italic toggle=\"yes\">CACNA1A<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">ATP1A2<\/jats:italic>\n                    , in severe head trauma response, our results support a role for heterozygous deleterious mutations in genes implicated in neurological dysfunction and potentially increasing the risk of poor response to trivial head trauma.\n                  <\/jats:p>","DOI":"10.1089\/neu.2019.6962","type":"journal-article","created":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T03:00:42Z","timestamp":1585710042000},"page":"1870-1879","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Exploring Neuronal Vulnerability to Head Trauma Using a Whole Exome Approach"],"prefix":"10.1177","volume":"37","author":[{"given":"Omar","family":"Ibrahim","sequence":"first","affiliation":[{"name":"Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Science, Queensland University of Technology (QUT), Kelvin Grove, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi G.","family":"Sutherland","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Science, Queensland University of Technology (QUT), Kelvin Grove, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neven","family":"Maksemous","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Science, Queensland University of Technology (QUT), Kelvin Grove, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Smith","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Science, Queensland University of Technology (QUT), Kelvin Grove, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa M.","family":"Haupt","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Science, Queensland University of Technology (QUT), Kelvin Grove, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyn R.","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, Institute of Health and Biomedical Innovation, School of Biomedical Science, Queensland University of Technology (QUT), Kelvin Grove, Queensland, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,8,14]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13675"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2005.103.4.0707"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.196"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.1031"},{"issue":"80","key":"e_1_3_6_6_2","first-page":"1125","article-title":"Early seizures and cerebral oedema after trivial head trauma associated with the CACNA1A S218L mutation","author":"Terwindt G.","year":"2009","unstructured":"Terwindt G., , and van den Maagdenberg A. 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