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Identification of a novel CHN1 p.(Phe213Val) variant in a large Han Chinese family with congenital Duane retraction syndrome

Duane retraction syndrome (DRS) is a neuromuscular dysfunction of the eyes. Although many causative genes of DRS have been identified in Europe and the United States, few reports have been published in regard to Chinese DRS. The aim of the present study was to explore the genetic defect of DRS in a...

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Autores principales: Zhou, Tai-Cheng, Duan, Wen-Hua, Fu, Xiao-Lin, Zhu, Qin, Guo, Li-Yun, Zhou, Yuan, Hua, Zhi-Juan, Li, Xue-Jiao, Yang, Dong-Mei, Zhang, Jie-Ying, Yin, Jie, Zhang, Xiao-Fan, Zhou, Guang-Long, Hu, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531002/
https://www.ncbi.nlm.nih.gov/pubmed/33004823
http://dx.doi.org/10.1038/s41598-020-73190-1
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author Zhou, Tai-Cheng
Duan, Wen-Hua
Fu, Xiao-Lin
Zhu, Qin
Guo, Li-Yun
Zhou, Yuan
Hua, Zhi-Juan
Li, Xue-Jiao
Yang, Dong-Mei
Zhang, Jie-Ying
Yin, Jie
Zhang, Xiao-Fan
Zhou, Guang-Long
Hu, Min
author_facet Zhou, Tai-Cheng
Duan, Wen-Hua
Fu, Xiao-Lin
Zhu, Qin
Guo, Li-Yun
Zhou, Yuan
Hua, Zhi-Juan
Li, Xue-Jiao
Yang, Dong-Mei
Zhang, Jie-Ying
Yin, Jie
Zhang, Xiao-Fan
Zhou, Guang-Long
Hu, Min
author_sort Zhou, Tai-Cheng
collection PubMed
description Duane retraction syndrome (DRS) is a neuromuscular dysfunction of the eyes. Although many causative genes of DRS have been identified in Europe and the United States, few reports have been published in regard to Chinese DRS. The aim of the present study was to explore the genetic defect of DRS in a Chinese family. Exome sequencing was used to identify the disease-causing gene for the two affected family members. Ophthalmic and physical examinations, as well as genetic screenings for variants in chimerin 1 (CHN1), were performed for all family members. Functional analyses of a CHN1 variant in 293T cells included a Rac-GTP activation assay, α2-chimaerin translocation assay, and co-immunoprecipitation assay. Genetic analysis revealed a NM_001822.7: c.637T > G variant in the CHN1 gene, which resulted in the substitution of a highly conserved C1 domain with valine at codon 213 (NP_001813.1: p.(Phe213Val)) (ClinVar Accession Number: SCV001335305). In-silico analysis revealed that the p.(Phe213Val) substitution affected the protein stability and connections among the amino acids of CHN1 in terms of its tertiary protein structure. Functional studies indicated that the p.(Phe213Val) substitution reduced Rac-GTP activity and enhanced membrane translocation in response to phorbol-myristoyl acetate (PMA). Together with previous studies, our present findings demonstrate that CHN1 may be an important causative gene for different ethnicities with DRS.
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spelling pubmed-75310022020-10-06 Identification of a novel CHN1 p.(Phe213Val) variant in a large Han Chinese family with congenital Duane retraction syndrome Zhou, Tai-Cheng Duan, Wen-Hua Fu, Xiao-Lin Zhu, Qin Guo, Li-Yun Zhou, Yuan Hua, Zhi-Juan Li, Xue-Jiao Yang, Dong-Mei Zhang, Jie-Ying Yin, Jie Zhang, Xiao-Fan Zhou, Guang-Long Hu, Min Sci Rep Article Duane retraction syndrome (DRS) is a neuromuscular dysfunction of the eyes. Although many causative genes of DRS have been identified in Europe and the United States, few reports have been published in regard to Chinese DRS. The aim of the present study was to explore the genetic defect of DRS in a Chinese family. Exome sequencing was used to identify the disease-causing gene for the two affected family members. Ophthalmic and physical examinations, as well as genetic screenings for variants in chimerin 1 (CHN1), were performed for all family members. Functional analyses of a CHN1 variant in 293T cells included a Rac-GTP activation assay, α2-chimaerin translocation assay, and co-immunoprecipitation assay. Genetic analysis revealed a NM_001822.7: c.637T > G variant in the CHN1 gene, which resulted in the substitution of a highly conserved C1 domain with valine at codon 213 (NP_001813.1: p.(Phe213Val)) (ClinVar Accession Number: SCV001335305). In-silico analysis revealed that the p.(Phe213Val) substitution affected the protein stability and connections among the amino acids of CHN1 in terms of its tertiary protein structure. Functional studies indicated that the p.(Phe213Val) substitution reduced Rac-GTP activity and enhanced membrane translocation in response to phorbol-myristoyl acetate (PMA). Together with previous studies, our present findings demonstrate that CHN1 may be an important causative gene for different ethnicities with DRS. Nature Publishing Group UK 2020-10-01 /pmc/articles/PMC7531002/ /pubmed/33004823 http://dx.doi.org/10.1038/s41598-020-73190-1 Text en © The Author(s) 2020 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/.
spellingShingle Article
Zhou, Tai-Cheng
Duan, Wen-Hua
Fu, Xiao-Lin
Zhu, Qin
Guo, Li-Yun
Zhou, Yuan
Hua, Zhi-Juan
Li, Xue-Jiao
Yang, Dong-Mei
Zhang, Jie-Ying
Yin, Jie
Zhang, Xiao-Fan
Zhou, Guang-Long
Hu, Min
Identification of a novel CHN1 p.(Phe213Val) variant in a large Han Chinese family with congenital Duane retraction syndrome
title Identification of a novel CHN1 p.(Phe213Val) variant in a large Han Chinese family with congenital Duane retraction syndrome
title_full Identification of a novel CHN1 p.(Phe213Val) variant in a large Han Chinese family with congenital Duane retraction syndrome
title_fullStr Identification of a novel CHN1 p.(Phe213Val) variant in a large Han Chinese family with congenital Duane retraction syndrome
title_full_unstemmed Identification of a novel CHN1 p.(Phe213Val) variant in a large Han Chinese family with congenital Duane retraction syndrome
title_short Identification of a novel CHN1 p.(Phe213Val) variant in a large Han Chinese family with congenital Duane retraction syndrome
title_sort identification of a novel chn1 p.(phe213val) variant in a large han chinese family with congenital duane retraction syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531002/
https://www.ncbi.nlm.nih.gov/pubmed/33004823
http://dx.doi.org/10.1038/s41598-020-73190-1
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