{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:46:31Z","timestamp":1785836791999,"version":"3.56.0"},"reference-count":12,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100022720","name":"Fondazione Regionale per la Ricerca Biomedica","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022720","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pathogenic variants in\n                    <jats:italic>CACNA1C<\/jats:italic>\n                    have been associated with cardiac arrhythmias and neurodevelopmental disorders, occasionally accompanied by movement disorders. Here we report the case of a 66\u2010year\u2010old female patient with combined dystonia\u2010parkinsonism carrying a pathogenic\n                    <jats:italic>CACNA1C<\/jats:italic>\n                    variant. Neurological examination revealed painful tremulous cervical dystonia, blepharospasm, divergent strabismus, hypomimia, and mild dystonic posturing of left hand, action tremor, and bradykinesia of the upper limbs. Botulinum toxin type A injections provided only partial relief of cervical dystonia, so the patient underwent bilateral Deep Brain Stimulation of Globus Pallidus Internus (GPi\u2010DBS), which resulted in dystonia improvement. Genetic analysis identified an extremely rare heterozygous nonsense variant in the\n                    <jats:italic>CACNA1C<\/jats:italic>\n                    gene (NM_199460.3: c.481C\u2009&gt;\u2009T; NP_955630.3: p.Arg161*), predicted to introduce a premature stop codon resulting in early protein truncation. Haploinsufficiency is a known disease mechanism for this gene. This variant has previously been reported in two individuals with neurodevelopmental phenotypes. Based on ACMG guidelines, the variant was classified as pathogenic. Our findings suggest that\n                    <jats:italic>CACNA1C<\/jats:italic>\n                    variants may be associated with adult\u2010onset movement disorders, even in the absence of a prior history of neurodevelopmental disease. This case broadens the phenotypic spectrum within CACNA1C\u2010related disorders. GPi\u2010DBS may represent a valuable therapeutic option in selected cases.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70168","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T05:13:19Z","timestamp":1776143599000},"page":"2118-2121","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>\n                      <i>CACNA1C<\/i>\n                    <\/scp>\n                    \u2010Related Channelopathy Presenting With Adult\u2010Onset Combined Dystonia\u2010Parkinsonism: A Novel Neurological Presentation"],"prefix":"10.1002","volume":"200","author":[{"given":"Donatella","family":"Ottaviani","sequence":"first","affiliation":[{"name":"Neurology Unit Santa Maria del Carmine Hospital, Azienda Sanitaria Universitaria Integrata del Trentino (ASUIT)  Rovereto Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3347-7679","authenticated-orcid":false,"given":"Ruggero","family":"Bacchin","sequence":"additional","affiliation":[{"name":"Neurology Unit Santa Chiara Hospital, Azienda Sanitaria Universitaria Integrata del Trentino (ASUIT)  Trento Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlend","family":"Pje\u00e7i","sequence":"additional","affiliation":[{"name":"Neurology Unit Santa Chiara Hospital, Azienda Sanitaria Universitaria Integrata del Trentino (ASUIT)  Trento Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Chiara","family":"Malaguti","sequence":"additional","affiliation":[{"name":"Neurology Unit Santa Chiara Hospital, Azienda Sanitaria Universitaria Integrata del Trentino (ASUIT)  Trento 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Integrata del Trentino (ASUIT)  Trento Italy"},{"name":"Center for Mind\/Brain Sciences (CIMeC) University of Trento  Rovereto Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Dzinovic","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Klinikum Rechts der Isar, School of Medicine and Health Technical University of Munich  Munich Germany"},{"name":"Institute of Neurogenomics, Helmholtz Zentrum M\u00fcnchen  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8112-9153","authenticated-orcid":false,"given":"Michael","family":"Zech","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Klinikum Rechts der Isar, School of Medicine and Health Technical University of Munich  Munich Germany"},{"name":"Institute of Neurogenomics, Helmholtz Zentrum M\u00fcnchen  Munich Germany"},{"name":"Germany Institute for Advanced Study Technical University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6478-026X","authenticated-orcid":false,"given":"Alessio","family":"Di Fonzo","sequence":"additional","affiliation":[{"name":"Neurology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4720-9234","authenticated-orcid":false,"given":"Edoardo","family":"Monfrini","sequence":"additional","affiliation":[{"name":"Neurology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan 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