{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T21:18:55Z","timestamp":1775164735739,"version":"3.50.1"},"reference-count":62,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T00:00:00Z","timestamp":1496275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"IHS-GSK Pat Humphrey Research Fellowship 2002"},{"name":"National Fund for Scientific Research-Belgium, Special Research Funds of the University of Li\u00e8ge"},{"name":"Fonds Fr\u00e9d\u00e9ricq of the Faculty of Medicine-ULg"},{"name":"PAINCAGE FP7 Collaborative Project","award":["603191"],"award-info":[{"award-number":["603191"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Headache"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To search for differences in prevalence of a\n                      <jats:italic>CACNA1E<\/jats:italic>\n                      variant between migraine without aura, various phenotypes of migraine with aura, and healthy controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Familial hemiplegic migraine type 1 (FHM1) is associated with mutations in the\n                      <jats:italic>CACNA1A<\/jats:italic>\n                      gene coding for the alpha 1A (Ca\n                      <jats:sub>v<\/jats:sub>\n                      2.1) pore\u2010forming subunit of P\/Q voltage\u2010dependent Ca\n                      <jats:sup>2+<\/jats:sup>\n                      channels. These mutations are not found in the common forms of migraine with or without aura. The alpha 1E subunit (Ca\n                      <jats:sub>v<\/jats:sub>\n                      2.3) is the counterpart of Ca\n                      <jats:sub>v<\/jats:sub>\n                      2.1 in R\u2010type Ca\n                      <jats:sup>2+<\/jats:sup>\n                      channels, has different functional properties, and is encoded by the\n                      <jats:italic>CACNA1E<\/jats:italic>\n                      gene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      First, we performed a total exon sequencing of the\n                      <jats:italic>CACNA1E<\/jats:italic>\n                      gene in three probands selected because they had no abnormalities in the three FHM genes. In a patient suffering from basilar\u2010type migraine, we identified a single nucleotide polymorphism (SNP) in exon 20 of the\n                      <jats:italic>CACNA1E<\/jats:italic>\n                      gene (Asp859Glu \u2013 rs35737760; Minor Allele Frequency 0.2241) hitherto not studied in migraine. In a second step, we determined its occurrence in four groups by direct sequencing on blood genomic DNA: migraine patients without aura (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200924), with typical aura (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200955), complex neurological auras (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200919; hemiplegic aura:\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200915; brain stem aura:\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20094), and healthy controls (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009102).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The Asp859Glu \u2013\n                      <jats:italic>rs35737760<\/jats:italic>\n                      SNP of the\n                      <jats:italic>CACNA1E<\/jats:italic>\n                      gene was present in 12.7% of control subjects and in 20.4% of the total migraine group. In the migraine group it was significantly over\u2010represented in patients with complex neurological auras (42.1%), OR 4.98 (95% CI: 1.69\u201014.67, uncorrected\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.005, Bonferroni\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.030, 2\u2010tailed Fisher's exact test). There was no significant difference between migraine with typical aura (10.9%) and controls.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We identified a polymorphism in exon 20 of the\n                      <jats:italic>CACNA1E<\/jats:italic>\n                      gene (Asp859Glu \u2013\n                      <jats:italic>rs35737760<\/jats:italic>\n                      ) that is more prevalent in hemiplegic and brain stem aura migraine. This missense variant causes a change from aspartate to glutamate at position 859 of the Ca\n                      <jats:sub>v<\/jats:sub>\n                      2.3 protein and might modulate the function of R\u2010type Ca\n                      <jats:sup>2+<\/jats:sup>\n                      channels. It could thus be relevant for migraine with complex neurological aura, although this remains to be proven.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.13107","type":"journal-article","created":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T23:18:47Z","timestamp":1496359127000},"page":"1136-1144","source":"Crossref","is-referenced-by-count":16,"title":["Possible Involvement of the\n                    <i>CACNA1E<\/i>\n                    Gene in Migraine: A Search for Single Nucleotide Polymorphism in Different Clinical Phenotypes"],"prefix":"10.1111","volume":"57","author":[{"given":"Anna","family":"Ambrosini","sequence":"first","affiliation":[{"name":"IRCCS Neuromed Pozzilli (Isernia) Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mara","family":"D'Onofrio","sequence":"additional","affiliation":[{"name":"European Brain Research Institute \u201cRita Levi Montalcini,\u201d Rome Italy"},{"name":"CNR Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Gabriella","family":"Buzzi","sequence":"additional","affiliation":[{"name":"IRCCS Santa Lucia Foundation Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Arisi","sequence":"additional","affiliation":[{"name":"European Brain Research Institute \u201cRita Levi Montalcini,\u201d Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaetano S.","family":"Grieco","sequence":"additional","affiliation":[{"name":"C. 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