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Exome Sequencing Identifies a Novel Sorting Nexin 14 Gene Mutation Causing Cerebellar Atrophy and Intellectual Disability
The autosomal recessive cerebellar ataxias (ARCA) affect both the central and the peripheral nervous systems. They are also characterized by a relatively high level of genetic heterogeneity with well over 40 genes already implicated. The present study aimed to identify the gene mutation responsible...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220403/ https://www.ncbi.nlm.nih.gov/pubmed/30473892 http://dx.doi.org/10.1155/2018/6737938 |
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author | Al-Hashmi, Nadia Mohammed, Mohammed Al-Kathir, Salim Al-Yarubi, Naeema Scott, Patrick |
author_facet | Al-Hashmi, Nadia Mohammed, Mohammed Al-Kathir, Salim Al-Yarubi, Naeema Scott, Patrick |
author_sort | Al-Hashmi, Nadia |
collection | PubMed |
description | The autosomal recessive cerebellar ataxias (ARCA) affect both the central and the peripheral nervous systems. They are also characterized by a relatively high level of genetic heterogeneity with well over 40 genes already implicated. The present study aimed to identify the gene mutation responsible for a complex phenotype comprising cerebellar ataxia and intellectual disability segregating in an Omani consanguineous family. Homozygosity-guided exome data analysis identified a novel frameshift mutation (c.2319_2322del) within the sorting nexin 14 gene (SNX14), which predicts complete absence of the SNX14 encoded protein. Segregation within the family of the sequence variation is consistent with its pathogenic role. Importantly, loss-of-function mutations in SNX14 have recently been described as a cause of a clinically distinguishable recessive syndrome consisting of cerebellar atrophy, ataxia, coarsened facial features, and intellectual disability. This study expands the genetic diversity of ataxia genes in the Omani population and have important implications for the clinical and molecular diagnosis of this condition in affected individuals. |
format | Online Article Text |
id | pubmed-6220403 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-62204032018-11-25 Exome Sequencing Identifies a Novel Sorting Nexin 14 Gene Mutation Causing Cerebellar Atrophy and Intellectual Disability Al-Hashmi, Nadia Mohammed, Mohammed Al-Kathir, Salim Al-Yarubi, Naeema Scott, Patrick Case Rep Genet Case Report The autosomal recessive cerebellar ataxias (ARCA) affect both the central and the peripheral nervous systems. They are also characterized by a relatively high level of genetic heterogeneity with well over 40 genes already implicated. The present study aimed to identify the gene mutation responsible for a complex phenotype comprising cerebellar ataxia and intellectual disability segregating in an Omani consanguineous family. Homozygosity-guided exome data analysis identified a novel frameshift mutation (c.2319_2322del) within the sorting nexin 14 gene (SNX14), which predicts complete absence of the SNX14 encoded protein. Segregation within the family of the sequence variation is consistent with its pathogenic role. Importantly, loss-of-function mutations in SNX14 have recently been described as a cause of a clinically distinguishable recessive syndrome consisting of cerebellar atrophy, ataxia, coarsened facial features, and intellectual disability. This study expands the genetic diversity of ataxia genes in the Omani population and have important implications for the clinical and molecular diagnosis of this condition in affected individuals. Hindawi 2018-10-24 /pmc/articles/PMC6220403/ /pubmed/30473892 http://dx.doi.org/10.1155/2018/6737938 Text en Copyright © 2018 Nadia Al-Hashmi et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Case Report Al-Hashmi, Nadia Mohammed, Mohammed Al-Kathir, Salim Al-Yarubi, Naeema Scott, Patrick Exome Sequencing Identifies a Novel Sorting Nexin 14 Gene Mutation Causing Cerebellar Atrophy and Intellectual Disability |
title | Exome Sequencing Identifies a Novel Sorting Nexin 14 Gene Mutation Causing Cerebellar Atrophy and Intellectual Disability |
title_full | Exome Sequencing Identifies a Novel Sorting Nexin 14 Gene Mutation Causing Cerebellar Atrophy and Intellectual Disability |
title_fullStr | Exome Sequencing Identifies a Novel Sorting Nexin 14 Gene Mutation Causing Cerebellar Atrophy and Intellectual Disability |
title_full_unstemmed | Exome Sequencing Identifies a Novel Sorting Nexin 14 Gene Mutation Causing Cerebellar Atrophy and Intellectual Disability |
title_short | Exome Sequencing Identifies a Novel Sorting Nexin 14 Gene Mutation Causing Cerebellar Atrophy and Intellectual Disability |
title_sort | exome sequencing identifies a novel sorting nexin 14 gene mutation causing cerebellar atrophy and intellectual disability |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220403/ https://www.ncbi.nlm.nih.gov/pubmed/30473892 http://dx.doi.org/10.1155/2018/6737938 |
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