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Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration
(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 at...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958857/ https://www.ncbi.nlm.nih.gov/pubmed/33801522 http://dx.doi.org/10.3390/ijms22052505 |
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author | Sancho, Paula Andrés-Bordería, Amparo Gorría-Redondo, Nerea Llano, Katia Martínez-Rubio, Dolores Yoldi-Petri, María Eugenia Blumkin, Luba Rodríguez de la Fuente, Pablo Gil-Ortiz, Fernando Fernández-Murga, Leonor Sánchez-Monteagudo, Ana Lupo, Vincenzo Pérez-Dueñas, Belén Espinós, Carmen Aguilera-Albesa, Sergio |
author_facet | Sancho, Paula Andrés-Bordería, Amparo Gorría-Redondo, Nerea Llano, Katia Martínez-Rubio, Dolores Yoldi-Petri, María Eugenia Blumkin, Luba Rodríguez de la Fuente, Pablo Gil-Ortiz, Fernando Fernández-Murga, Leonor Sánchez-Monteagudo, Ana Lupo, Vincenzo Pérez-Dueñas, Belén Espinós, Carmen Aguilera-Albesa, Sergio |
author_sort | Sancho, Paula |
collection | PubMed |
description | (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. |
format | Online Article Text |
id | pubmed-7958857 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79588572021-03-16 Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration Sancho, Paula Andrés-Bordería, Amparo Gorría-Redondo, Nerea Llano, Katia Martínez-Rubio, Dolores Yoldi-Petri, María Eugenia Blumkin, Luba Rodríguez de la Fuente, Pablo Gil-Ortiz, Fernando Fernández-Murga, Leonor Sánchez-Monteagudo, Ana Lupo, Vincenzo Pérez-Dueñas, Belén Espinós, Carmen Aguilera-Albesa, Sergio Int J Mol Sci Article (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. MDPI 2021-03-02 /pmc/articles/PMC7958857/ /pubmed/33801522 http://dx.doi.org/10.3390/ijms22052505 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sancho, Paula Andrés-Bordería, Amparo Gorría-Redondo, Nerea Llano, Katia Martínez-Rubio, Dolores Yoldi-Petri, María Eugenia Blumkin, Luba Rodríguez de la Fuente, Pablo Gil-Ortiz, Fernando Fernández-Murga, Leonor Sánchez-Monteagudo, Ana Lupo, Vincenzo Pérez-Dueñas, Belén Espinós, Carmen Aguilera-Albesa, Sergio Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration |
title | Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration |
title_full | Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration |
title_fullStr | Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration |
title_full_unstemmed | Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration |
title_short | Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration |
title_sort | expanding the β-iii spectrin-associated phenotypes toward non-progressive congenital ataxias with neurodegeneration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958857/ https://www.ncbi.nlm.nih.gov/pubmed/33801522 http://dx.doi.org/10.3390/ijms22052505 |
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