open access

Vol 25, No 1 (2018)
Original articles — Basic science and experimental cardiology
Published online: 2017-09-06
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Novel and heteroplasmic mutations in mitochondrial tRNA genes in Brugada syndrome

Mahsasadat Fallah Tafti, Mehri Khatami, Shiva Rezaei, Mohammad Mehdi Heidari, Mehdi Hadadzadeh
DOI: 10.5603/CJ.a2017.0104
·
Pubmed: 28980288
·
Cardiol J 2018;25(1):113-119.

open access

Vol 25, No 1 (2018)
Original articles — Basic science and experimental cardiology
Published online: 2017-09-06

Abstract

Background: Brugada syndrome (BrS) is a rare cardiac arrhythmia characterized by sudden death associated with electrocardiogram patterns characterized by incomplete right bundle-branch block and ST-segment elevations in the anterior precordial leads. This syndrome predominantly is seen in younger males with structurally normal hearts. Mitochondrial variants particularly mt-tRNA mutations, are hot spots that lead to cardiological disorders. Previous studies have shown that mutations in mitochondrial tRNA genes play an important causal or modifying role in BrS. The present study aims to evaluate the involvement of mitochondrial tRNA genes in arrhythmogenic BrS.

Methods: In this study, 40 Iranian patients were investigated for the presence of the mutations in 6 mitochondrial tRNA genes (tRNA Ile, Met, Gln, Asn, Ala and Trp) by PCR-SSCP analysis.

Results: There were 4 mutations in tRNA genes, that for first time, were found in BrS patients and these mutations were not in controls. Three of them were heteroplasmic and located in tRNAGln (T4377A) and tRNAMet (G4407A and C4456T) which were assessed as pathogenic mutations. A homo­plasmic variant (5580T > C) in tRNATrp gene was located within the junction region between tRNATrp and tRNAAla genes. This mutation may disturb the processing of mt-tRNATrp.

Conclusions: The results of this study suggest that mutations in mitochondrial tRNA genes might lead to deficiencies in translational process of critical proteins of the respiratory chain and potentially lead to BrS in Iranian subjects. (Cardiol J 2018; 25, 1: 113–119)

Abstract

Background: Brugada syndrome (BrS) is a rare cardiac arrhythmia characterized by sudden death associated with electrocardiogram patterns characterized by incomplete right bundle-branch block and ST-segment elevations in the anterior precordial leads. This syndrome predominantly is seen in younger males with structurally normal hearts. Mitochondrial variants particularly mt-tRNA mutations, are hot spots that lead to cardiological disorders. Previous studies have shown that mutations in mitochondrial tRNA genes play an important causal or modifying role in BrS. The present study aims to evaluate the involvement of mitochondrial tRNA genes in arrhythmogenic BrS.

Methods: In this study, 40 Iranian patients were investigated for the presence of the mutations in 6 mitochondrial tRNA genes (tRNA Ile, Met, Gln, Asn, Ala and Trp) by PCR-SSCP analysis.

Results: There were 4 mutations in tRNA genes, that for first time, were found in BrS patients and these mutations were not in controls. Three of them were heteroplasmic and located in tRNAGln (T4377A) and tRNAMet (G4407A and C4456T) which were assessed as pathogenic mutations. A homo­plasmic variant (5580T > C) in tRNATrp gene was located within the junction region between tRNATrp and tRNAAla genes. This mutation may disturb the processing of mt-tRNATrp.

Conclusions: The results of this study suggest that mutations in mitochondrial tRNA genes might lead to deficiencies in translational process of critical proteins of the respiratory chain and potentially lead to BrS in Iranian subjects. (Cardiol J 2018; 25, 1: 113–119)

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Keywords

cardiac arrhythmia, Brugada syndrome, mitochondrial tRNAs, variations

About this article
Title

Novel and heteroplasmic mutations in mitochondrial tRNA genes in Brugada syndrome

Journal

Cardiology Journal

Issue

Vol 25, No 1 (2018)

Pages

113-119

Published online

2017-09-06

DOI

10.5603/CJ.a2017.0104

Pubmed

28980288

Bibliographic record

Cardiol J 2018;25(1):113-119.

Keywords

cardiac arrhythmia
Brugada syndrome
mitochondrial tRNAs
variations

Authors

Mahsasadat Fallah Tafti
Mehri Khatami
Shiva Rezaei
Mohammad Mehdi Heidari
Mehdi Hadadzadeh

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