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Two novel missense variants in SPTBN2 likely associated with spinocerebellar ataxia type 5
INTRODUCTION: Spinocerebellar ataxias (SCAs) are a heterozygous group of neurodegenerative disorders. Spinocerebellar ataxia type 5 (SCA5) is a rare autosomal-dominant ataxia with pure cerebellum involvement. The clinical characteristics are limb and gait ataxia, trunk ataxia, sensory deficits, abno...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8642373/ https://www.ncbi.nlm.nih.gov/pubmed/33797620 http://dx.doi.org/10.1007/s10072-021-05204-3 |
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author | Bian, Xianli Wang, Shang Jin, Suqin Xu, Shunliang Zhang, Hong Wang, Dewei Shang, Wei Wang, Ping |
author_facet | Bian, Xianli Wang, Shang Jin, Suqin Xu, Shunliang Zhang, Hong Wang, Dewei Shang, Wei Wang, Ping |
author_sort | Bian, Xianli |
collection | PubMed |
description | INTRODUCTION: Spinocerebellar ataxias (SCAs) are a heterozygous group of neurodegenerative disorders. Spinocerebellar ataxia type 5 (SCA5) is a rare autosomal-dominant ataxia with pure cerebellum involvement. The clinical characteristics are limb and gait ataxia, trunk ataxia, sensory deficits, abnormal eye movement, dysarthria, and hyperactive tendon reflexes. Spectrin beta nonerythrocytic 2 gene (SPTBN2), coding β-III spectrin protein, was identified to be associated with SCA5. To date, more than 19 variants of SPTBN2 have been reported. METHODS: A family and an apparently sporadic patient with ataxia and cerebellar atrophy were recruited from Shandong Province (China). To discover the disease-causing variants, capillary electrophoresis and targeted next-generation sequencing were performed in the proband of the family and the sporadic patient. The candidate variants were verified by Sanger sequencing and analyzed by bioinformatics software. RESULTS: In our study, we verified two novel heterozygous variants in SPTBN2 in a SCA pedigree and a sporadic patient. The proband of the pedigree and her mother presented with walking instability and progressively getting worse. The sporadic patient suffered from slurred speech, walking instability, and drinking water choking cough. MRI examination of the proband and sporadic patient both displayed moderate cerebellar atrophy. The variants identified were traditionally conserved and predicted probably damaging and disease-causing by bioinformatics analysis. CONCLUSION: We identified two novel heterozygous variants of SPTBN2 resulting in severe ataxia which further delineated the correlation between the genotype and phenotype of SCA5, and pathogenesis of variants in SPTBN2 should be further researched. |
format | Online Article Text |
id | pubmed-8642373 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-86423732021-12-17 Two novel missense variants in SPTBN2 likely associated with spinocerebellar ataxia type 5 Bian, Xianli Wang, Shang Jin, Suqin Xu, Shunliang Zhang, Hong Wang, Dewei Shang, Wei Wang, Ping Neurol Sci Original Article INTRODUCTION: Spinocerebellar ataxias (SCAs) are a heterozygous group of neurodegenerative disorders. Spinocerebellar ataxia type 5 (SCA5) is a rare autosomal-dominant ataxia with pure cerebellum involvement. The clinical characteristics are limb and gait ataxia, trunk ataxia, sensory deficits, abnormal eye movement, dysarthria, and hyperactive tendon reflexes. Spectrin beta nonerythrocytic 2 gene (SPTBN2), coding β-III spectrin protein, was identified to be associated with SCA5. To date, more than 19 variants of SPTBN2 have been reported. METHODS: A family and an apparently sporadic patient with ataxia and cerebellar atrophy were recruited from Shandong Province (China). To discover the disease-causing variants, capillary electrophoresis and targeted next-generation sequencing were performed in the proband of the family and the sporadic patient. The candidate variants were verified by Sanger sequencing and analyzed by bioinformatics software. RESULTS: In our study, we verified two novel heterozygous variants in SPTBN2 in a SCA pedigree and a sporadic patient. The proband of the pedigree and her mother presented with walking instability and progressively getting worse. The sporadic patient suffered from slurred speech, walking instability, and drinking water choking cough. MRI examination of the proband and sporadic patient both displayed moderate cerebellar atrophy. The variants identified were traditionally conserved and predicted probably damaging and disease-causing by bioinformatics analysis. CONCLUSION: We identified two novel heterozygous variants of SPTBN2 resulting in severe ataxia which further delineated the correlation between the genotype and phenotype of SCA5, and pathogenesis of variants in SPTBN2 should be further researched. Springer International Publishing 2021-04-02 2021 /pmc/articles/PMC8642373/ /pubmed/33797620 http://dx.doi.org/10.1007/s10072-021-05204-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Bian, Xianli Wang, Shang Jin, Suqin Xu, Shunliang Zhang, Hong Wang, Dewei Shang, Wei Wang, Ping Two novel missense variants in SPTBN2 likely associated with spinocerebellar ataxia type 5 |
title | Two novel missense variants in SPTBN2 likely associated with spinocerebellar ataxia type 5 |
title_full | Two novel missense variants in SPTBN2 likely associated with spinocerebellar ataxia type 5 |
title_fullStr | Two novel missense variants in SPTBN2 likely associated with spinocerebellar ataxia type 5 |
title_full_unstemmed | Two novel missense variants in SPTBN2 likely associated with spinocerebellar ataxia type 5 |
title_short | Two novel missense variants in SPTBN2 likely associated with spinocerebellar ataxia type 5 |
title_sort | two novel missense variants in sptbn2 likely associated with spinocerebellar ataxia type 5 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8642373/ https://www.ncbi.nlm.nih.gov/pubmed/33797620 http://dx.doi.org/10.1007/s10072-021-05204-3 |
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