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Int. J. Mol. Sci. 2015, 16(10), 25773-25787;

Rare Titin (TTN) Variants in Diseases Associated with Sudden Cardiac Death

Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona 17190, Spain
Medical Science Department, School of Medicine, University of Girona, Girona 17071, Spain
Cardiovascular Genetics Clinic, Hospital Josep Trueta, Girona 17007, Spain
These authors contributed equally to this work.
Author to whom correspondence should be addressed.
Academic Editor: Emil Alexov
Received: 22 July 2015 / Revised: 12 October 2015 / Accepted: 19 October 2015 / Published: 27 October 2015
(This article belongs to the Collection Human Single Nucleotide Polymorphisms and Disease Diagnostics)
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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. View Full-Text
Keywords: pediatric; juvenile; sudden cardiac death; genetics; next-generation sequencing; forensics; titin pediatric; juvenile; sudden cardiac death; genetics; next-generation sequencing; forensics; titin

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Campuzano, O.; Sanchez-Molero, O.; Mademont-Soler, I.; Riuró, H.; Allegue, C.; Coll, M.; Pérez-Serra, A.; Mates, J.; Picó, F.; Iglesias, A.; Brugada, R. Rare Titin (TTN) Variants in Diseases Associated with Sudden Cardiac Death. Int. J. Mol. Sci. 2015, 16, 25773-25787.

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