Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration
| العنوان: | Expanding the β-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration |
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| المؤلفون: | 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, Universitat Autònoma de Barcelona |
| المساهمون: | Institut Català de la Salut, [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, Vall d'Hebron Barcelona Hospital Campus |
| المصدر: | International Journal of Molecular Sciences Volume 22 Issue 5 International Journal of Molecular Sciences, Vol 22, Iss 2505, p 2505 (2021) Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Scientia |
| بيانات النشر: | MDPI, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Proband, Pathology, Protein Conformation, Sequence Homology, SPTBN2 gene, b-III spectrin, 030105 genetics & heredity, Fluid-attenuated inversion recovery, Cohort Studies, lcsh:Chemistry, Non-progressive congenital ataxia, 0302 clinical medicine, β-III spectrin, Spectrin, enfermedades del sistema nervioso::enfermedades neurodegenerativas [ENFERMEDADES], Age of Onset, Child, lcsh:QH301-705.5, Spectroscopy, Otros calificadores::Otros calificadores::/genética [Otros calificadores], Neurodegeneration, neurodegeneration, Neurodegenerative Diseases, non-progressive congenital ataxia, Syndrome, General Medicine, Phenotype, Hypotonia, Computer Science Applications, Nervous System Diseases::Neurodegenerative Diseases [DISEASES], Spinocerebellar ataxia, medicine.symptom, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Cerebellar Ataxia, Neuroimaging, Biology, Catalysis, Article, Inorganic Chemistry, 03 medical and health sciences, Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebellar Diseases::Cerebellar Ataxia [DISEASES], Other subheadings::Other subheadings::/genetics [Other subheadings], medicine, Humans, Amino Acid Sequence, Physical and Theoretical Chemistry, Molecular Biology, Genetic Association Studies, Organic Chemistry, medicine.disease, Hyperintensity, Sistema nerviós - Degeneració - Aspectes genètics, lcsh:Biology (General), lcsh:QD1-999, enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::enfermedades cerebelosas::ataxia cerebelosa [ENFERMEDADES], Mutation, 030217 neurology & neurosurgery |
| الوصف: | (1) Background: A non-progressive congenital ataxia (NPCA) phenotype caused by b-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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::33d864457d3f818299c2330160bb9c62Test http://europepmc.org/articles/PMC7958857Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....33d864457d3f818299c2330160bb9c62 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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