Cargando…
Rare Titin (TTN) Variants in Diseases Associated with Sudden Cardiac Death
A leading cause of death in western countries is sudden cardiac death, and can be associated with genetic disease. Next-generation sequencing has allowed thorough analysis of genes associated with this entity, including, most recently, titin. We aimed to identify potentially pathogenic genetic varia...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632826/ https://www.ncbi.nlm.nih.gov/pubmed/26516846 http://dx.doi.org/10.3390/ijms161025773 |
_version_ | 1782399105689976832 |
---|---|
author | Campuzano, Oscar Sanchez-Molero, Olallo Mademont-Soler, Irene Riuró, Helena Allegue, Catarina Coll, Monica Pérez-Serra, Alexandra Mates, Jesus Picó, Ferran Iglesias, Anna Brugada, Ramon |
author_facet | Campuzano, Oscar Sanchez-Molero, Olallo Mademont-Soler, Irene Riuró, Helena Allegue, Catarina Coll, Monica Pérez-Serra, Alexandra Mates, Jesus Picó, Ferran Iglesias, Anna Brugada, Ramon |
author_sort | Campuzano, Oscar |
collection | PubMed |
description | A leading cause of death in western countries is sudden cardiac death, and can be associated with genetic disease. Next-generation sequencing has allowed thorough analysis of genes associated with this entity, including, most recently, titin. We aimed to identify potentially pathogenic genetic variants in titin. A total of 1126 samples were analyzed using a custom sequencing panel including major genes related to sudden cardiac death. Our cohort was divided into three groups: 432 cases from patients with cardiomyopathies, 130 cases from patients with channelopathies, and 564 post-mortem samples from individuals showing anatomical healthy hearts and non-conclusive causes of death after comprehensive autopsy. None of the patients included had definite pathogenic variants in the genes analyzed by our custom cardio-panel. Retrospective analysis comparing the in-house database and available public databases also was performed. We identified 554 rare variants in titin, 282 of which were novel. Seven were previously reported as pathogenic. Of these 554 variants, 493 were missense variants, 233 of which were novel. Of all variants identified, 399 were unique and 155 were identified at least twice. No definite pathogenic variants were identified in any of genes analyzed. We identified rare, mostly novel, titin variants that seem to play a potentially pathogenic role in sudden cardiac death. Additional studies should be performed to clarify the role of these variants in sudden cardiac death. |
format | Online Article Text |
id | pubmed-4632826 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-46328262015-11-23 Rare Titin (TTN) Variants in Diseases Associated with Sudden Cardiac Death Campuzano, Oscar Sanchez-Molero, Olallo Mademont-Soler, Irene Riuró, Helena Allegue, Catarina Coll, Monica Pérez-Serra, Alexandra Mates, Jesus Picó, Ferran Iglesias, Anna Brugada, Ramon Int J Mol Sci Article A leading cause of death in western countries is sudden cardiac death, and can be associated with genetic disease. Next-generation sequencing has allowed thorough analysis of genes associated with this entity, including, most recently, titin. We aimed to identify potentially pathogenic genetic variants in titin. A total of 1126 samples were analyzed using a custom sequencing panel including major genes related to sudden cardiac death. Our cohort was divided into three groups: 432 cases from patients with cardiomyopathies, 130 cases from patients with channelopathies, and 564 post-mortem samples from individuals showing anatomical healthy hearts and non-conclusive causes of death after comprehensive autopsy. None of the patients included had definite pathogenic variants in the genes analyzed by our custom cardio-panel. Retrospective analysis comparing the in-house database and available public databases also was performed. We identified 554 rare variants in titin, 282 of which were novel. Seven were previously reported as pathogenic. Of these 554 variants, 493 were missense variants, 233 of which were novel. Of all variants identified, 399 were unique and 155 were identified at least twice. No definite pathogenic variants were identified in any of genes analyzed. We identified rare, mostly novel, titin variants that seem to play a potentially pathogenic role in sudden cardiac death. Additional studies should be performed to clarify the role of these variants in sudden cardiac death. MDPI 2015-10-27 /pmc/articles/PMC4632826/ /pubmed/26516846 http://dx.doi.org/10.3390/ijms161025773 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Campuzano, Oscar Sanchez-Molero, Olallo Mademont-Soler, Irene Riuró, Helena Allegue, Catarina Coll, Monica Pérez-Serra, Alexandra Mates, Jesus Picó, Ferran Iglesias, Anna Brugada, Ramon Rare Titin (TTN) Variants in Diseases Associated with Sudden Cardiac Death |
title | Rare Titin (TTN) Variants in Diseases Associated with Sudden Cardiac Death |
title_full | Rare Titin (TTN) Variants in Diseases Associated with Sudden Cardiac Death |
title_fullStr | Rare Titin (TTN) Variants in Diseases Associated with Sudden Cardiac Death |
title_full_unstemmed | Rare Titin (TTN) Variants in Diseases Associated with Sudden Cardiac Death |
title_short | Rare Titin (TTN) Variants in Diseases Associated with Sudden Cardiac Death |
title_sort | rare titin (ttn) variants in diseases associated with sudden cardiac death |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632826/ https://www.ncbi.nlm.nih.gov/pubmed/26516846 http://dx.doi.org/10.3390/ijms161025773 |
work_keys_str_mv | AT campuzanooscar raretitinttnvariantsindiseasesassociatedwithsuddencardiacdeath AT sanchezmoleroolallo raretitinttnvariantsindiseasesassociatedwithsuddencardiacdeath AT mademontsolerirene raretitinttnvariantsindiseasesassociatedwithsuddencardiacdeath AT riurohelena raretitinttnvariantsindiseasesassociatedwithsuddencardiacdeath AT alleguecatarina raretitinttnvariantsindiseasesassociatedwithsuddencardiacdeath AT collmonica raretitinttnvariantsindiseasesassociatedwithsuddencardiacdeath AT perezserraalexandra raretitinttnvariantsindiseasesassociatedwithsuddencardiacdeath AT matesjesus raretitinttnvariantsindiseasesassociatedwithsuddencardiacdeath AT picoferran raretitinttnvariantsindiseasesassociatedwithsuddencardiacdeath AT iglesiasanna raretitinttnvariantsindiseasesassociatedwithsuddencardiacdeath AT brugadaramon raretitinttnvariantsindiseasesassociatedwithsuddencardiacdeath |