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Case Report: A Novel Variant c.2262+3A>T of the SCN5A Gene Results in Intron Retention Associated With Incessant Ventricular Tachycardias
Objective: Voltage-gated sodium channel Na(v)1.5 encoded by the SCN5A gene plays crucial roles in cardiac electrophysiology. Previous genetic studies have shown that mutations in SCN5A are associated with multiple inherited cardiac arrhythmias. Here, we investigated the molecular defect in a Chinese...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371685/ https://www.ncbi.nlm.nih.gov/pubmed/34422849 http://dx.doi.org/10.3389/fmed.2021.659119 |
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author | Yin, Jie Zhou, Jia Chen, Jinlong Xu, Ting Zhang, Zhongman Zhang, Han Yuan, Chang Cheng, Xueying Qin, Yuming Zheng, Bixia Wang, Chunli Yang, Shiwei Jia, Zhanjun |
author_facet | Yin, Jie Zhou, Jia Chen, Jinlong Xu, Ting Zhang, Zhongman Zhang, Han Yuan, Chang Cheng, Xueying Qin, Yuming Zheng, Bixia Wang, Chunli Yang, Shiwei Jia, Zhanjun |
author_sort | Yin, Jie |
collection | PubMed |
description | Objective: Voltage-gated sodium channel Na(v)1.5 encoded by the SCN5A gene plays crucial roles in cardiac electrophysiology. Previous genetic studies have shown that mutations in SCN5A are associated with multiple inherited cardiac arrhythmias. Here, we investigated the molecular defect in a Chinese boy with clinical manifestations of arrhythmias. Methods: Gene variations were screened using whole-exome sequencing and validated by direct Sanger sequencing. A minigene assay and reverse transcription PCR (RT-PCR) were performed to confirm the effects of splice variants in vitro. Western blot analysis was carried out to determine whether the c.2262+3A>T variant produced a truncated protein. Results: By genetic analysis, we identified a novel splice variant c.2262+3A>T in SCN5A gene in a Chinese boy with incessant ventricular tachycardias (VT). This variant was predicted to activate a new cryptic splice donor site and was identified by in silico analysis. The variant retained 79 bp at the 5′ end of intron 14 in the mature mRNA. Furthermore, the mutant transcript that created a premature stop codon at 818 amino acids [p.(R818(*))] could be produced as a truncated protein. Conclusion: We verified the pathogenic effect of splicing variant c.2262+3A>T, which disturbed the normal mRNA splicing and caused a truncated protein, suggesting that splice variants play an important role in the molecular basis of early onset incessant ventricular tachycardias, and careful molecular profiling of these patients will be essential for future effective personalized treatment options. |
format | Online Article Text |
id | pubmed-8371685 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83716852021-08-19 Case Report: A Novel Variant c.2262+3A>T of the SCN5A Gene Results in Intron Retention Associated With Incessant Ventricular Tachycardias Yin, Jie Zhou, Jia Chen, Jinlong Xu, Ting Zhang, Zhongman Zhang, Han Yuan, Chang Cheng, Xueying Qin, Yuming Zheng, Bixia Wang, Chunli Yang, Shiwei Jia, Zhanjun Front Med (Lausanne) Medicine Objective: Voltage-gated sodium channel Na(v)1.5 encoded by the SCN5A gene plays crucial roles in cardiac electrophysiology. Previous genetic studies have shown that mutations in SCN5A are associated with multiple inherited cardiac arrhythmias. Here, we investigated the molecular defect in a Chinese boy with clinical manifestations of arrhythmias. Methods: Gene variations were screened using whole-exome sequencing and validated by direct Sanger sequencing. A minigene assay and reverse transcription PCR (RT-PCR) were performed to confirm the effects of splice variants in vitro. Western blot analysis was carried out to determine whether the c.2262+3A>T variant produced a truncated protein. Results: By genetic analysis, we identified a novel splice variant c.2262+3A>T in SCN5A gene in a Chinese boy with incessant ventricular tachycardias (VT). This variant was predicted to activate a new cryptic splice donor site and was identified by in silico analysis. The variant retained 79 bp at the 5′ end of intron 14 in the mature mRNA. Furthermore, the mutant transcript that created a premature stop codon at 818 amino acids [p.(R818(*))] could be produced as a truncated protein. Conclusion: We verified the pathogenic effect of splicing variant c.2262+3A>T, which disturbed the normal mRNA splicing and caused a truncated protein, suggesting that splice variants play an important role in the molecular basis of early onset incessant ventricular tachycardias, and careful molecular profiling of these patients will be essential for future effective personalized treatment options. Frontiers Media S.A. 2021-08-04 /pmc/articles/PMC8371685/ /pubmed/34422849 http://dx.doi.org/10.3389/fmed.2021.659119 Text en Copyright © 2021 Yin, Zhou, Chen, Xu, Zhang, Zhang, Yuan, Cheng, Qin, Zheng, Wang, Yang and Jia. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Medicine Yin, Jie Zhou, Jia Chen, Jinlong Xu, Ting Zhang, Zhongman Zhang, Han Yuan, Chang Cheng, Xueying Qin, Yuming Zheng, Bixia Wang, Chunli Yang, Shiwei Jia, Zhanjun Case Report: A Novel Variant c.2262+3A>T of the SCN5A Gene Results in Intron Retention Associated With Incessant Ventricular Tachycardias |
title | Case Report: A Novel Variant c.2262+3A>T of the SCN5A Gene Results in Intron Retention Associated With Incessant Ventricular Tachycardias |
title_full | Case Report: A Novel Variant c.2262+3A>T of the SCN5A Gene Results in Intron Retention Associated With Incessant Ventricular Tachycardias |
title_fullStr | Case Report: A Novel Variant c.2262+3A>T of the SCN5A Gene Results in Intron Retention Associated With Incessant Ventricular Tachycardias |
title_full_unstemmed | Case Report: A Novel Variant c.2262+3A>T of the SCN5A Gene Results in Intron Retention Associated With Incessant Ventricular Tachycardias |
title_short | Case Report: A Novel Variant c.2262+3A>T of the SCN5A Gene Results in Intron Retention Associated With Incessant Ventricular Tachycardias |
title_sort | case report: a novel variant c.2262+3a>t of the scn5a gene results in intron retention associated with incessant ventricular tachycardias |
topic | Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371685/ https://www.ncbi.nlm.nih.gov/pubmed/34422849 http://dx.doi.org/10.3389/fmed.2021.659119 |
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