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Coexistence of Two Rare Genetic Variants in Canonical and Non-canonical Exons of SCN5A: A Potential Source of Misinterpretation
Primary cardiac channelopathies are a group of diseases wherein the role of DNA testing in aiding diagnosis and treatment-based decision-making is gaining increasing attention. However, in some cases, evaluating the pathogenicity of new variants is still challenging. We report an accurate multistage...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450431/ https://www.ncbi.nlm.nih.gov/pubmed/34552620 http://dx.doi.org/10.3389/fgene.2021.722291 |
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author | Shestak, Anna G. Makarov, Leonid M. Komoliatova, Vera N. Kolesnikova, Irina V. Skorodumova, Liubov O. Generozov, Edward V. Zaklyazminskaya, Elena V. |
author_facet | Shestak, Anna G. Makarov, Leonid M. Komoliatova, Vera N. Kolesnikova, Irina V. Skorodumova, Liubov O. Generozov, Edward V. Zaklyazminskaya, Elena V. |
author_sort | Shestak, Anna G. |
collection | PubMed |
description | Primary cardiac channelopathies are a group of diseases wherein the role of DNA testing in aiding diagnosis and treatment-based decision-making is gaining increasing attention. However, in some cases, evaluating the pathogenicity of new variants is still challenging. We report an accurate multistage assessment of a rare genetic variant in the SCN5A gene using next-generation sequencing (NGS) techniques and Sanger sequencing. Female sportsman (14 years old) underwent genetic counseling and DNA testing due to QT interval prolongation registered during ECG Holter monitoring. Genetic testing of the proband was performed in two independent laboratories. Primary DNA testing was performed by WES using the Ion Proton(TM) System. Target panel sequencing of 11 genes was performed using PGM Ion Torrent. Search for variants in non-canonical and canonical exons 6 was performed by Sanger sequencing. The cascade familial screening and control re-sequencing were provided for proband with identified genetic variant p.S216L (g.38655290G>A, NM_198056.2:c.647C>T, and rs41276525) in the canonical exon 6 of the SCN5A gene after receiving data from another laboratory. Control Sanger and NGS sequencing revealed the absence p.S216L in the canonical exon 6 and confirmed the presence of p.S216L (g.38655522G>A, c.647C>T, and rs201002736) in the non-canonical exon 6 of the SCN5A gene. The identified variant was re-interpreted. The non-canonical transcripts of the exon 6 of the SCN5A gene is poorly represented in cardiac tissue (gnomAD). The detected variant was found in proband’s healthy mother. The correct interpretation of genetic data requires close cooperation between clinicians and researchers. It can help to avoid financial costs and stress for proband’s and families. |
format | Online Article Text |
id | pubmed-8450431 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84504312021-09-21 Coexistence of Two Rare Genetic Variants in Canonical and Non-canonical Exons of SCN5A: A Potential Source of Misinterpretation Shestak, Anna G. Makarov, Leonid M. Komoliatova, Vera N. Kolesnikova, Irina V. Skorodumova, Liubov O. Generozov, Edward V. Zaklyazminskaya, Elena V. Front Genet Genetics Primary cardiac channelopathies are a group of diseases wherein the role of DNA testing in aiding diagnosis and treatment-based decision-making is gaining increasing attention. However, in some cases, evaluating the pathogenicity of new variants is still challenging. We report an accurate multistage assessment of a rare genetic variant in the SCN5A gene using next-generation sequencing (NGS) techniques and Sanger sequencing. Female sportsman (14 years old) underwent genetic counseling and DNA testing due to QT interval prolongation registered during ECG Holter monitoring. Genetic testing of the proband was performed in two independent laboratories. Primary DNA testing was performed by WES using the Ion Proton(TM) System. Target panel sequencing of 11 genes was performed using PGM Ion Torrent. Search for variants in non-canonical and canonical exons 6 was performed by Sanger sequencing. The cascade familial screening and control re-sequencing were provided for proband with identified genetic variant p.S216L (g.38655290G>A, NM_198056.2:c.647C>T, and rs41276525) in the canonical exon 6 of the SCN5A gene after receiving data from another laboratory. Control Sanger and NGS sequencing revealed the absence p.S216L in the canonical exon 6 and confirmed the presence of p.S216L (g.38655522G>A, c.647C>T, and rs201002736) in the non-canonical exon 6 of the SCN5A gene. The identified variant was re-interpreted. The non-canonical transcripts of the exon 6 of the SCN5A gene is poorly represented in cardiac tissue (gnomAD). The detected variant was found in proband’s healthy mother. The correct interpretation of genetic data requires close cooperation between clinicians and researchers. It can help to avoid financial costs and stress for proband’s and families. Frontiers Media S.A. 2021-09-06 /pmc/articles/PMC8450431/ /pubmed/34552620 http://dx.doi.org/10.3389/fgene.2021.722291 Text en Copyright © 2021 Shestak, Makarov, Komoliatova, Kolesnikova, Skorodumova, Generozov and Zaklyazminskaya. 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 | Genetics Shestak, Anna G. Makarov, Leonid M. Komoliatova, Vera N. Kolesnikova, Irina V. Skorodumova, Liubov O. Generozov, Edward V. Zaklyazminskaya, Elena V. Coexistence of Two Rare Genetic Variants in Canonical and Non-canonical Exons of SCN5A: A Potential Source of Misinterpretation |
title | Coexistence of Two Rare Genetic Variants in Canonical and Non-canonical Exons of SCN5A: A Potential Source of Misinterpretation |
title_full | Coexistence of Two Rare Genetic Variants in Canonical and Non-canonical Exons of SCN5A: A Potential Source of Misinterpretation |
title_fullStr | Coexistence of Two Rare Genetic Variants in Canonical and Non-canonical Exons of SCN5A: A Potential Source of Misinterpretation |
title_full_unstemmed | Coexistence of Two Rare Genetic Variants in Canonical and Non-canonical Exons of SCN5A: A Potential Source of Misinterpretation |
title_short | Coexistence of Two Rare Genetic Variants in Canonical and Non-canonical Exons of SCN5A: A Potential Source of Misinterpretation |
title_sort | coexistence of two rare genetic variants in canonical and non-canonical exons of scn5a: a potential source of misinterpretation |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450431/ https://www.ncbi.nlm.nih.gov/pubmed/34552620 http://dx.doi.org/10.3389/fgene.2021.722291 |
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