Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

Supraventricular tachycardias, conduction disease, and cardiomyopathy in 3 families with the same rare variant in TNNI3K (p.Glu768Lys)

Svitlana Podliesna 1 Julian Delanne 2 Lindsey Miller 3 David Tester 4 Merujan Uzunyan 3 Shoji Yano 3 Mischa Klerk 1 Bryan Cannon 4 Apichai Khongphatthanayothin 3 Gabriel Laurent 5 Geraldine Bertaux 5 Sylvie Falcon-Eicher 5 Shengnan Wu 6 Hai-Yun Yen 6 Hanlin Gao 6 Arthur Wilde 1 Laurence Faivre 2, 7, 8 Michael Ackerman 4 Elisabeth Lodder 1 Connie Bezzina 1, *
* Auteur correspondant
1 Department of Clinical and Experimental Cardiology (Heart Center, Academic Medical Center, Amsterdam)
2 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)
3 Keck School of Medicine [Los Angeles]
4 Mayo Clinic
5 Service de Cardiologie [CHU de Dijon]
6 Fulgent Genetics (Temple City, California)
7 Equipe GAD (LNC - U1231)
LNC - Lipides - Nutrition - Cancer [Dijon - U1231]
8 GIMI - Genetic and Immunology Medical Institute
Abstract : Background Rare genetic variants in TNNI3K encoding troponin-I interacting kinase have been linked to a distinct syndrome consisting primarily of supraventricular tachycardias and variably expressed conduction disturbance and dilated cardiomyopathy in 2 families. Objective The purpose of this study was to identify new genetic variants associated with inherited supraventricular tachycardias, cardiac conduction disease, and cardiomyopathy. Methods We conducted next generation sequencing in 3 independent multigenerational families with atrial/junctional tachycardia with or without conduction disturbance, dilated cardiomyopathy, and sudden death. We also assessed the effect of identified variant on protein autophosphorylation. Results In this study, we uncovered the same ultra-rare genetic variant in TNNI3K (c.2302G>A, p.Glu768Lys), which co-segregated with disease features in all affected individuals (n = 23) from all 3 families. TNNI3K harboring the TNNI3K-p.Glu768Lys variant displayed enhanced kinase activity, in line with expectations from previous mouse studies that demonstrated increased conduction indices and procardiomyopathic effects with increased levels of Tnni3k. Conclusion This study corroborates further the causal link between rare genetic variation in TNNI3K and this distinct complex phenotype, and points to enhanced kinase activity of TNNI3K as the underlying pathobiological mechanism.
Keywords : Conduction disease Dilated cardiomyopathy Genetics Kinase Rare variant Supraventricular tachycardia TNNI3K
Type de document :
Article dans une revue
Liste complète des métadonnées
https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01990544
Contributeur : Lnc - Université de Bourgogne <>
Soumis le : mercredi 23 janvier 2019 - 11:04:07
Dernière modification le : vendredi 5 février 2021 - 03:45:21

Identifiants

Collections

UNIV-BOURGOGNE | CGFL | FNCLCC | LNC-UMR866 | LNC-GAD

Citation

Svitlana Podliesna, Julian Delanne, Lindsey Miller, David Tester, Merujan Uzunyan, et al.. Supraventricular tachycardias, conduction disease, and cardiomyopathy in 3 families with the same rare variant in TNNI3K (p.Glu768Lys). Heart Rhythm, Elsevier, 2019, 16 (1), pp.98-105. ⟨10.1016/j.hrthm.2018.07.015⟩. ⟨hal-01990544⟩

Exporter

BibTeX TEI DC DCterms EndNote

Partager

Métriques

Consultations de la notice

116