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Identification of a Splicing Mutation in ITPR1 via WES in a Chinese Early-Onset Spinocerebellar Ataxia Family

Mutations in the inositol 1,4,5-triphosphate receptor type 1 gene (ITPR1) lead to SCA15, SCA16, and SCA29. To date, only a few families with SCA29 have been reported. A three-generation Chinese family including four affected persons and two unaffected persons were enrolled in this study. We conducte...

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Autores principales: Wang, Li, Hao, Ying, Yu, Peng, Cao, Zhenhua, Zhang, Jin, Zhang, Xin, Chen, Yuanyuan, Zhang, Hao, Gu, Weihong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966481/
https://www.ncbi.nlm.nih.gov/pubmed/29196976
http://dx.doi.org/10.1007/s12311-017-0896-z
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author Wang, Li
Hao, Ying
Yu, Peng
Cao, Zhenhua
Zhang, Jin
Zhang, Xin
Chen, Yuanyuan
Zhang, Hao
Gu, Weihong
author_facet Wang, Li
Hao, Ying
Yu, Peng
Cao, Zhenhua
Zhang, Jin
Zhang, Xin
Chen, Yuanyuan
Zhang, Hao
Gu, Weihong
author_sort Wang, Li
collection PubMed
description Mutations in the inositol 1,4,5-triphosphate receptor type 1 gene (ITPR1) lead to SCA15, SCA16, and SCA29. To date, only a few families with SCA29 have been reported. A three-generation Chinese family including four affected persons and two unaffected persons were enrolled in this study. We conducted whole-exome sequencing (WES) of the proband DNA initially to find the causal gene. We ascertained the family with autosomal dominant type of congenital nonprogressive cerebellar ataxia (CNPCA) associated with delayed motor and cognitive impairment. WES study was performed with two patients and identified c.1207-2A–T transition, in exon 14 of ITPR1, which was a splicing mutation. Sanger sequencing showed that four patients within this family carried the mutation and two unaffected members did not carry it. The results showed that the novel splicing mutation of ITPR1 was the causative gene for SCA29. In conclusion, we identified a novel SCA29 causative splicing mutation of ITPR1 in a Chinese family. We suggest ITPR1 gene analysis shall be a priority for diagnosis of patients with early-onset CNPCA. Our study demonstrated that whole-exome sequencing might rapidly improve the diagnosis of genetic ataxias. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12311-017-0896-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-59664812018-06-04 Identification of a Splicing Mutation in ITPR1 via WES in a Chinese Early-Onset Spinocerebellar Ataxia Family Wang, Li Hao, Ying Yu, Peng Cao, Zhenhua Zhang, Jin Zhang, Xin Chen, Yuanyuan Zhang, Hao Gu, Weihong Cerebellum Original Paper Mutations in the inositol 1,4,5-triphosphate receptor type 1 gene (ITPR1) lead to SCA15, SCA16, and SCA29. To date, only a few families with SCA29 have been reported. A three-generation Chinese family including four affected persons and two unaffected persons were enrolled in this study. We conducted whole-exome sequencing (WES) of the proband DNA initially to find the causal gene. We ascertained the family with autosomal dominant type of congenital nonprogressive cerebellar ataxia (CNPCA) associated with delayed motor and cognitive impairment. WES study was performed with two patients and identified c.1207-2A–T transition, in exon 14 of ITPR1, which was a splicing mutation. Sanger sequencing showed that four patients within this family carried the mutation and two unaffected members did not carry it. The results showed that the novel splicing mutation of ITPR1 was the causative gene for SCA29. In conclusion, we identified a novel SCA29 causative splicing mutation of ITPR1 in a Chinese family. We suggest ITPR1 gene analysis shall be a priority for diagnosis of patients with early-onset CNPCA. Our study demonstrated that whole-exome sequencing might rapidly improve the diagnosis of genetic ataxias. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12311-017-0896-z) contains supplementary material, which is available to authorized users. Springer US 2017-12-01 2018 /pmc/articles/PMC5966481/ /pubmed/29196976 http://dx.doi.org/10.1007/s12311-017-0896-z Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Paper
Wang, Li
Hao, Ying
Yu, Peng
Cao, Zhenhua
Zhang, Jin
Zhang, Xin
Chen, Yuanyuan
Zhang, Hao
Gu, Weihong
Identification of a Splicing Mutation in ITPR1 via WES in a Chinese Early-Onset Spinocerebellar Ataxia Family
title Identification of a Splicing Mutation in ITPR1 via WES in a Chinese Early-Onset Spinocerebellar Ataxia Family
title_full Identification of a Splicing Mutation in ITPR1 via WES in a Chinese Early-Onset Spinocerebellar Ataxia Family
title_fullStr Identification of a Splicing Mutation in ITPR1 via WES in a Chinese Early-Onset Spinocerebellar Ataxia Family
title_full_unstemmed Identification of a Splicing Mutation in ITPR1 via WES in a Chinese Early-Onset Spinocerebellar Ataxia Family
title_short Identification of a Splicing Mutation in ITPR1 via WES in a Chinese Early-Onset Spinocerebellar Ataxia Family
title_sort identification of a splicing mutation in itpr1 via wes in a chinese early-onset spinocerebellar ataxia family
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966481/
https://www.ncbi.nlm.nih.gov/pubmed/29196976
http://dx.doi.org/10.1007/s12311-017-0896-z
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