Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration
Sancho, Paula (Centro de Investigación Príncipe Felipe (València))
Andrés-Bordería, Amparo (Universitat de València)
Gorría-Redondo, Nerea (Complejo Hospitalario de Navarra)
Llano, Katia (Complejo Hospitalario de Navarra)
Martínez-Rubio, Dolores (Centro de Investigación Príncipe Felipe (València))
Yoldi-Petri, María Eugenia (Complejo Hospitalario de Navarra)
Blumkin, Luba (Tel-Aviv University)
Rodríguez de la Fuente, Pablo (Complejo Hospitalario de Navarra)
Gil-Ortiz, Fernando (ALBA Laboratori de Llum de Sincrotró)
Fernández-Murga, Leonor (Hospital Arnau de Vilanova (Lleida, Catalunya))
Sánchez-Monteagudo, Ana (Centro de Investigación Príncipe Felipe (València))
Lupo, Vincenzo (Centro de Investigación Príncipe Felipe (València))
Pérez-Dueñas, Belén (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Espinós, Carmen (Centro de Investigación Príncipe Felipe (València))
Aguilera-Albesa, Sergio (Navarrabiomed-Fundación Miguel Servet)
Universitat Autònoma de Barcelona

Date:	2021
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.
Grants:	Instituto de Salud Carlos III PI18/00147 Ministerio de Educación, Cultura y Deporte FPU15/00964
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	SPTBN2 gene ; β-III spectrin ; Non-progressive congenital ataxia ; Neurodegeneration
Published in:	International journal of molecular sciences, Vol. 22 (march 2021) , ISSN 1422-0067

DOI: 10.3390/ijms22052505
PMID: 33801522

11 p, 2.7 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Experimental sciences > The ALBA Synchrotron
Articles > Research articles
Articles > Published articles