{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T18:13:18Z","timestamp":1789409598221,"version":"build-2803163510"},"reference-count":220,"publisher":"American Society for Clinical Investigation","issue":"18","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:p>\n                    Rare monogenic subtypes of migraine with aura, which include an autosomal dominant form of hemiplegic migraine (HM), are caused by exonic mutations whose functional consequences can be studied in cellular and animal models of the disease. This allows investigation of the neurobiological mechanisms at the molecular, cellular, and circuit level. Here, I review current knowledge of the genetics and pathophysiology of HM. After considering the genes whose mutations cause familial HM (FHM) and discussing how the encoded proteins are affected by the mutations, I consider the mouse models generated by introducing human FHM mutations in the orthologous genes,\n                    <jats:italic>Cana1a<\/jats:italic>\n                    ,\n                    <jats:italic>Atp1a2<\/jats:italic>\n                    , and\n                    <jats:italic>Scna1a<\/jats:italic>\n                    . I discuss their phenotypes, highlighting their shared increased susceptibility to experimentally induced cortical spreading depression (CSD, the phenomenon which underlies migraine aura and may trigger the headache mechanisms) and migraine-relevant pain behaviors. I examine the alterations in the cerebral cortex and the mechanisms underlying the facilitation of CSD in the mouse models as well as the alterations in the trigeminovascular pain pathway and their possible contributions to migraine-relevant pain phenotypes. Finally, I discuss the translational implications of the pathogenic mechanisms of CSD facilitation.\n                  <\/jats:p>","DOI":"10.1172\/jci208001","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T18:01:18Z","timestamp":1789408878000},"source":"Crossref","is-referenced-by-count":0,"title":["Hemiplegic migraine: genetics and pathophysiology"],"prefix":"10.1172","volume":"136","author":[{"given":"Daniela","family":"Pietrobon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102417738202"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-030212-183717"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.01.029"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00034.2015"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3770"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0373-15.2015"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2021.01.002"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-080422-105509"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-025-01128-0"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1126\/science.adl0544"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-019-00142-7"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-823356-6.00012-3"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(24)00026-7"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70048-5"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2020-322850"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81373-2"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/ng1081"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)66786-4"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181f25e8f"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000295670.01629.5a"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004966"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-023-01547-8"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000200352"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00025.2020"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200107053450103"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.50.4.1105"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl334"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-2982.2008.01599.x"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1177\/0333102418761041"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3390\/cells9112368"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012947"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv317"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000590"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv310"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.04.014"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2019-106640"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03255-5"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3390\/genes16070807"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-14176-4"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1008705107"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000474"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-020-04961-x"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1177\/0333102413484988"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awag109"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2012.11.012"},{"key":"B46","unstructured":"Cooper DN, et al. 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