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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorSancho, Paula
dc.contributor.authorAndrés-Bordería, Amparo
dc.contributor.authorGorría-Redondo, Nerea
dc.contributor.authorLlano, Katia
dc.contributor.authorMartínez-Rubio, Dolores
dc.contributor.authorYoldi-Petri, María Eugenia
dc.contributor.authorPerez Dueñas, Belen
dc.date.accessioned2021-11-19T13:16:30Z
dc.date.available2021-11-19T13:16:30Z
dc.date.issued2021-03-02
dc.identifier.citationSancho P, Andrés-Bordería A, Gorría-Redondo N, Llano K, Martínez-Rubio D, Yoldi-Petri ME, et al. Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration. Int J Mol Sci. 2021 Mar 2;22(5):2505.
dc.identifier.issn1422-0067
dc.identifier.urihttp://hdl.handle.net/11351/6571
dc.descriptionSPTBN2 gene; Neurodegeneration; Non-progressive congenital ataxia
dc.description.abstract(1) Background: A non-progressive congenital ataxia (NPCA) phenotype caused by β-III spectrin (SPTBN2) mutations has emerged, mimicking spinocerebellar ataxia, autosomal recessive type 14 (SCAR14). The pattern of inheritance, however, resembles that of autosomal dominant classical spinocerebellar ataxia type 5 (SCA5). (2) Methods: In-depth phenotyping of two boys studied by a customized gene panel. Candidate variants were sought by structural modeling and protein expression. An extensive review of the literature was conducted in order to better characterize the SPTBN2-associated NPCA. (3) Results: Patients exhibited an NPCA with hypotonia, developmental delay, cerebellar syndrome, and cognitive deficits. Both probands presented with progressive global cerebellar volume loss in consecutive cerebral magnetic resonance imaging studies, characterized by decreasing midsagittal vermis relative diameter measurements. Cortical hyperintensities were observed on fluid-attenuated inversion recovery (FLAIR) images, suggesting a neurodegenerative process. Each patient carried a novel de novo SPTBN2 substitution: c.193A > G (p.K65E) or c.764A > G (p.D255G). Modeling and protein expression revealed that both mutations might be deleterious. (4) Conclusions: The reported findings contribute to a better understanding of the SPTBN2-associated phenotype. The mutations may preclude proper structural organization of the actin spectrin-based membrane skeleton, which, in turn, is responsible for the underlying disease mechanism.
dc.language.isoeng
dc.publisherMDPI
dc.relation.ispartofseriesInternational Journal of Molecular Sciences;22(5)
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectSistema nerviós - Degeneració - Aspectes genètics
dc.subject.meshNeurodegenerative Diseases
dc.subject.mesh/genetics
dc.subject.meshCerebellar Ataxia
dc.subject.mesh/genetics
dc.titleExpanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.3390/ijms22052505
dc.subject.decsenfermedades neurodegenerativas
dc.subject.decs/genética
dc.subject.decsataxia cerebelosa
dc.subject.decs/genética
dc.relation.publishversionhttps://doi.org/10.3390/ijms22052505
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Sancho P, Martínez-Rubio D] Unit of Rare Neurodegenerative Diseases, Centro de Investigación Príncipe Felipe (CIPF), 46012 Valencia, Spain. [Andrés-Bordería A] Unit of Rare Neurodegenerative Diseases, Centro de Investigación Príncipe Felipe (CIPF), 46012 Valencia, Spain. Department of Physiology, Faculty of Medicine and Dentistry, University of Valencia, 46010 Valencia, Spain. [Gorría-Redondo N, Yoldi-Petri ME] Pediatric Neurology Unit, Department of Pediatrics, Complejo Hospitalario de Navarra, 31008 Pamplona, Spain. [Pérez-Dueñas B] Grup de Recerca en Neurologia Pediàtrica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain
dc.identifier.pmid33801522
dc.identifier.wos000628287200001
dc.relation.projectidinfo:eu-repo/grantAgreement/ES/PE2013-2016/PI18%2F00147
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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