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A novel phenotype with splicing mutation identified in a Chinese family with desminopathy

BACKGROUND: Desminopathy, a hereditary myofibrillar myopathy, mainly results from the desmin gene (DES) mutations. Desminopathy involves various phenotypes, mainly including different cardiomyopathies, skeletal myopathy, and arrhythmia. Combined with genotype, it helps us precisely diagnose and trea...

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Autores principales: Fan, Peng, Lu, Chao-Xia, Dong, Xue-Qi, Zhu, Di, Yang, Kun-Qi, Liu, Ke-Qiang, Zhang, Di, Zhang, Ying, Meng, Xu, Tan, Hui-Qiong, Yu, Li-Tian, Dou, Ke-Fei, Liu, Ya-Xin, Zhang, Xue, Zhou, Xian-Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer Health 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365268/
https://www.ncbi.nlm.nih.gov/pubmed/30614851
http://dx.doi.org/10.1097/CM9.0000000000000001
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author Fan, Peng
Lu, Chao-Xia
Dong, Xue-Qi
Zhu, Di
Yang, Kun-Qi
Liu, Ke-Qiang
Zhang, Di
Zhang, Ying
Meng, Xu
Tan, Hui-Qiong
Yu, Li-Tian
Dou, Ke-Fei
Liu, Ya-Xin
Zhang, Xue
Zhou, Xian-Liang
author_facet Fan, Peng
Lu, Chao-Xia
Dong, Xue-Qi
Zhu, Di
Yang, Kun-Qi
Liu, Ke-Qiang
Zhang, Di
Zhang, Ying
Meng, Xu
Tan, Hui-Qiong
Yu, Li-Tian
Dou, Ke-Fei
Liu, Ya-Xin
Zhang, Xue
Zhou, Xian-Liang
author_sort Fan, Peng
collection PubMed
description BACKGROUND: Desminopathy, a hereditary myofibrillar myopathy, mainly results from the desmin gene (DES) mutations. Desminopathy involves various phenotypes, mainly including different cardiomyopathies, skeletal myopathy, and arrhythmia. Combined with genotype, it helps us precisely diagnose and treat for desminopathy. METHODS: Sanger sequencing was used to characterize DES variation, and then a minigene assay was used to verify the effect of splice-site mutation on pre-mRNA splicing. Phenotypes were analyzed based on clinical characteristics associated with desminopathy. RESULTS: A splicing mutation (c.735+1G>T) in DES was detected in the proband. A minigene assay revealed skipping of the whole exon 3 and transcription of abnormal pre-mRNA lacking 32 codons. Another affected family member who carried the identical mutation, was identified with a novel phenotype of desminopathy, non-compaction of ventricular myocardium. There were 2 different phenotypes varied in cardiomyopathy and skeletal myopathy among the 2 patients, but no significant correlation between genotype and phenotype was identified. CONCLUSIONS: We reported a novel phenotype with a splicing mutation in DES, enlarging the spectrum of phenotype in desminopathy. Molecular studies of desminopathy should promote our understanding of its pathogenesis and provide a precise molecular diagnosis of this disorder, facilitating clinical prevention and treatment at an early stage.
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spelling pubmed-63652682019-02-20 A novel phenotype with splicing mutation identified in a Chinese family with desminopathy Fan, Peng Lu, Chao-Xia Dong, Xue-Qi Zhu, Di Yang, Kun-Qi Liu, Ke-Qiang Zhang, Di Zhang, Ying Meng, Xu Tan, Hui-Qiong Yu, Li-Tian Dou, Ke-Fei Liu, Ya-Xin Zhang, Xue Zhou, Xian-Liang Chin Med J (Engl) Original Articles BACKGROUND: Desminopathy, a hereditary myofibrillar myopathy, mainly results from the desmin gene (DES) mutations. Desminopathy involves various phenotypes, mainly including different cardiomyopathies, skeletal myopathy, and arrhythmia. Combined with genotype, it helps us precisely diagnose and treat for desminopathy. METHODS: Sanger sequencing was used to characterize DES variation, and then a minigene assay was used to verify the effect of splice-site mutation on pre-mRNA splicing. Phenotypes were analyzed based on clinical characteristics associated with desminopathy. RESULTS: A splicing mutation (c.735+1G>T) in DES was detected in the proband. A minigene assay revealed skipping of the whole exon 3 and transcription of abnormal pre-mRNA lacking 32 codons. Another affected family member who carried the identical mutation, was identified with a novel phenotype of desminopathy, non-compaction of ventricular myocardium. There were 2 different phenotypes varied in cardiomyopathy and skeletal myopathy among the 2 patients, but no significant correlation between genotype and phenotype was identified. CONCLUSIONS: We reported a novel phenotype with a splicing mutation in DES, enlarging the spectrum of phenotype in desminopathy. Molecular studies of desminopathy should promote our understanding of its pathogenesis and provide a precise molecular diagnosis of this disorder, facilitating clinical prevention and treatment at an early stage. Wolters Kluwer Health 2019-01-20 2019-01-07 /pmc/articles/PMC6365268/ /pubmed/30614851 http://dx.doi.org/10.1097/CM9.0000000000000001 Text en Copyright © 2019 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license. http://creativecommons.org/licenses/by-nc-nd/4.0 This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0
spellingShingle Original Articles
Fan, Peng
Lu, Chao-Xia
Dong, Xue-Qi
Zhu, Di
Yang, Kun-Qi
Liu, Ke-Qiang
Zhang, Di
Zhang, Ying
Meng, Xu
Tan, Hui-Qiong
Yu, Li-Tian
Dou, Ke-Fei
Liu, Ya-Xin
Zhang, Xue
Zhou, Xian-Liang
A novel phenotype with splicing mutation identified in a Chinese family with desminopathy
title A novel phenotype with splicing mutation identified in a Chinese family with desminopathy
title_full A novel phenotype with splicing mutation identified in a Chinese family with desminopathy
title_fullStr A novel phenotype with splicing mutation identified in a Chinese family with desminopathy
title_full_unstemmed A novel phenotype with splicing mutation identified in a Chinese family with desminopathy
title_short A novel phenotype with splicing mutation identified in a Chinese family with desminopathy
title_sort novel phenotype with splicing mutation identified in a chinese family with desminopathy
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365268/
https://www.ncbi.nlm.nih.gov/pubmed/30614851
http://dx.doi.org/10.1097/CM9.0000000000000001
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