{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T11:58:56Z","timestamp":1779364736706,"version":"3.53.0"},"reference-count":44,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T00:00:00Z","timestamp":1620864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17\/00101"],"award-info":[{"award-number":["PI17\/00101"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["RTI2018-094809-B-I00"],"award-info":[{"award-number":["RTI2018-094809-B-I00"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["CEX2018-000792-M"],"award-info":[{"award-number":["CEX2018-000792-M"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019945","name":"Direcci\u00f3 General de Recerca, Generalitat de Catalunya","doi-asserted-by":"publisher","award":["PERIS SLT008\/18\/00194"],"award-info":[{"award-number":["PERIS SLT008\/18\/00194"]}],"id":[{"id":"10.13039\/501100019945","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The CACNA1A gene encodes the pore-forming \u03b11A subunit of the voltage-gated CaV2.1 Ca2+ channel, essential in neurotransmission, especially in Purkinje cells. Mutations in CACNA1A result in great clinical heterogeneity with progressive symptoms, paroxysmal events or both. During infancy, clinical and neuroimaging findings may be unspecific, and no dysmorphic features have been reported. We present the clinical, radiological and evolutionary features of three patients with congenital ataxia, one of them carrying a new variant. We report the structural localization of variants and their expected functional consequences. There was an improvement in cerebellar syndrome over time despite a cerebellar atrophy progression, inconsistent response to acetazolamide and positive response to methylphenidate. The patients shared distinctive facial gestalt: oval face, prominent forehead, hypertelorism, downslanting palpebral fissures and narrow nasal bridge. The two \u03b11A affected residues are fully conserved throughout evolution and among the whole human CaV channel family. They contribute to the channel pore and the voltage sensor segment. According to structural data analysis and available functional characterization, they are expected to exert gain- (F1394L) and loss-of-function (R1664Q\/R1669Q) effect, respectively. Among the CACNA1A-related phenotypes, our results suggest that non-progressive congenital ataxia is associated with developmental delay and dysmorphic features, constituting a recognizable syndromic neurodevelopmental disorder.<\/jats:p>","DOI":"10.3390\/ijms22105180","type":"journal-article","created":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T03:28:36Z","timestamp":1620962916000},"page":"5180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["CACNA1A Mutations Causing Early Onset Ataxia: Profiling Clinical, Dysmorphic and Structural-Functional Findings"],"prefix":"10.3390","volume":"22","author":[{"given":"Antonio F.","family":"Mart\u00ednez-Monseny","sequence":"first","affiliation":[{"name":"Department of Genetic and Molecular Medicine, Institut de Recerca, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Edo","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Physiology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00eddac","family":"Casas-Alba","sequence":"additional","affiliation":[{"name":"Department of Genetic and Molecular Medicine, Institut de Recerca, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3524-8052","authenticated-orcid":false,"given":"Merc\u00e8","family":"Izquierdo-Serra","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Physiology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merc\u00e8","family":"Bolasell","sequence":"additional","affiliation":[{"name":"Department of Genetic and Molecular Medicine, Institut de Recerca, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Conejo","sequence":"additional","affiliation":[{"name":"Pediatric Department, Complejo Asistencial de Burgos, 09006 Burgos, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loreto","family":"Martorell","sequence":"additional","affiliation":[{"name":"Department of Genetic and Molecular Medicine, Institut de Recerca, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"U-703 Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, 08002 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Muchart","sequence":"additional","affiliation":[{"name":"Pediatric Radiology Department, Institut de Recerca Sant Joan de D\u00e9u, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Carrera","sequence":"additional","affiliation":[{"name":"Neuropediatric Department, Institut de Recerca Sant Joan de D\u00e9u, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos I.","family":"Ortez","sequence":"additional","affiliation":[{"name":"U-703 Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, 08002 Barcelona, Spain"},{"name":"Neuropediatric Department, Institut de Recerca Sant Joan de D\u00e9u, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Nascimento","sequence":"additional","affiliation":[{"name":"U-703 Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, 08002 Barcelona, Spain"},{"name":"Neuropediatric Department, Institut de Recerca Sant Joan de D\u00e9u, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baldo","family":"Oliva","sequence":"additional","affiliation":[{"name":"Structural Bioinformatics Lab, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2330-8449","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Fern\u00e1ndez-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Physiology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2056-2428","authenticated-orcid":false,"given":"Mercedes","family":"Serrano","sequence":"additional","affiliation":[{"name":"U-703 Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, 08002 Barcelona, Spain"},{"name":"Neuropediatric Department, Institut de Recerca Sant Joan de D\u00e9u, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s00424-010-0802-8","article-title":"CaV2.1 channelopathies","volume":"460","author":"Pietrobon","year":"2010","journal-title":"Pfl\u00fcgers Arch. 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