{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T16:28:03Z","timestamp":1783441683949,"version":"3.54.6"},"reference-count":69,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T00:00:00Z","timestamp":1700092800000},"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 (ISCIII)","doi-asserted-by":"publisher","award":["PI21\/00103"],"award-info":[{"award-number":["PI21\/00103"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III (ISCIII)","doi-asserted-by":"publisher","award":["FI19\/00072"],"award-info":[{"award-number":["FI19\/00072"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"European Union","doi-asserted-by":"publisher","award":["PI21\/00103"],"award-info":[{"award-number":["PI21\/00103"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"European Union","doi-asserted-by":"publisher","award":["FI19\/00072"],"award-info":[{"award-number":["FI19\/00072"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union\u2014European Social Fund (FSE)","award":["PI21\/00103"],"award-info":[{"award-number":["PI21\/00103"]}]},{"name":"European Union\u2014European Social Fund (FSE)","award":["FI19\/00072"],"award-info":[{"award-number":["FI19\/00072"]}]},{"name":"Generalitat Valenciana","award":["PI21\/00103"],"award-info":[{"award-number":["PI21\/00103"]}]},{"name":"Generalitat Valenciana","award":["FI19\/00072"],"award-info":[{"award-number":["FI19\/00072"]}]},{"name":"ERDF","award":["PI21\/00103"],"award-info":[{"award-number":["PI21\/00103"]}]},{"name":"ERDF","award":["FI19\/00072"],"award-info":[{"award-number":["FI19\/00072"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cerebellar atrophy (CA) is a frequent neuroimaging finding in paediatric neurology, usually associated with cerebellar ataxia. The list of genes involved in hereditary forms of CA is continuously growing and reveals its genetic complexity. We investigated ten cases with early-onset cerebellar involvement with and without ataxia by exome sequencing or by a targeted panel with 363 genes involved in ataxia or spastic paraplegia. Novel variants were investigated by in silico or experimental approaches. Seven probands carry causative variants in well-known genes associated with CA or cerebellar hypoplasia: SETX, CACNA1G, CACNA1A, CLN6, CPLANE1, and TBCD. The remaining three cases deserve special attention; they harbour variants in MAST1, PI4KA and CLK2 genes. MAST1 is responsible for an ultrarare condition characterised by global developmental delay and cognitive decline; our index case added ataxia to the list of concomitant associated symptoms. PIK4A is mainly related to hypomyelinating leukodystrophy; our proband presented with pure spastic paraplegia and normal intellectual capacity. Finally, in a patient who suffers from mild ataxia with oculomotor apraxia, the de novo novel CLK2 c.1120T&gt;C variant was found. The protein expression of the mutated protein was reduced, which may indicate instability that would affect its kinase activity.<\/jats:p>","DOI":"10.3390\/ijms242216400","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T07:11:27Z","timestamp":1700118687000},"page":"16400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9293-266X","authenticated-orcid":false,"given":"Dolores","family":"Mart\u00ednez-Rubio","sequence":"first","affiliation":[{"name":"Rare Neurodegenerative Diseases Laboratory, Valencia Biomedical Research Foundation, Centro de Investigaci\u00f3n Pr\u00edncipe Felipe (CIPF), 46012 Val\u00e8ncia, Spain"},{"name":"Joint Unit CIPF-IIS La Fe Rare Diseases, 46012 Val\u00e8ncia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9548-4359","authenticated-orcid":false,"given":"Isabel","family":"Hinarejos","sequence":"additional","affiliation":[{"name":"Rare Neurodegenerative Diseases Laboratory, Valencia Biomedical Research Foundation, Centro de Investigaci\u00f3n Pr\u00edncipe Felipe (CIPF), 46012 Val\u00e8ncia, Spain"},{"name":"Joint Unit CIPF-IIS La Fe Rare Diseases, 46012 Val\u00e8ncia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8537-1318","authenticated-orcid":false,"given":"Herminia","family":"Argente-Escrig","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Universitari Arnau de Vilanova, 46012 Val\u00e8ncia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8813-3515","authenticated-orcid":false,"given":"Clara","family":"Marco-Mar\u00edn","sequence":"additional","affiliation":[{"name":"Structural Enzymopathology Unit, Instituto de Biomedicina de Valencia (IBV), Consejo Superior de Investigaciones Cient\u00edficas (CSIC), 46022 Val\u00e8ncia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III (ISCIII), 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Ana","family":"Lozano","sequence":"additional","affiliation":[{"name":"Rare Neurodegenerative Diseases Laboratory, Valencia Biomedical Research Foundation, Centro de Investigaci\u00f3n Pr\u00edncipe Felipe (CIPF), 46012 Val\u00e8ncia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nerea","family":"Gorr\u00eda-Redondo","sequence":"additional","affiliation":[{"name":"Paediatric Neurology Unit, Department of Paediatrics, Hospital Universitario de Navarra, Navarrabiomed, 31008 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Lupo","sequence":"additional","affiliation":[{"name":"Rare Neurodegenerative Diseases Laboratory, Valencia Biomedical Research Foundation, Centro de Investigaci\u00f3n Pr\u00edncipe Felipe (CIPF), 46012 Val\u00e8ncia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0578-9568","authenticated-orcid":false,"given":"Itxaso","family":"Mart\u00ed-Carrera","sequence":"additional","affiliation":[{"name":"Paediatric Neurology Unit, Department of Paediatrics, Hospital Universitario Donostia, 20014 Donostia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8675-6823","authenticated-orcid":false,"given":"Concepci\u00f3n","family":"Miranda","sequence":"additional","affiliation":[{"name":"Paediatric Neurology Unit, Department of Paediatrics, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, 28027 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1599-8841","authenticated-orcid":false,"given":"Mar\u00eda","family":"V\u00e1zquez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Paediatric Neurology Unit, Department of Paediatrics, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, 28027 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asunci\u00f3n","family":"Garc\u00eda-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Paediatric Neurology Unit, Department of Paediatrics, Hospital Universitario Fundaci\u00f3n 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