Idiopathic ventricular fibrillation: a role of variants in the
hERG gene

a 2024

Idiopathic ventricular fibrillation: a role of variants in the hERG gene

BÉBAROVÁ, Markéta, Natálie JANKOVÁ, Olga ŠVECOVÁ, Martin KRÁL, Jana ZÍDKOVÁ et. al.

Basic information

Original name

Idiopathic ventricular fibrillation: a role of variants in the hERG gene

Authors

BÉBAROVÁ, Markéta (203 Czech Republic, guarantor, belonging to the institution), Natálie JANKOVÁ (203 Czech Republic, belonging to the institution), Olga ŠVECOVÁ (203 Czech Republic, belonging to the institution), Martin KRÁL (203 Czech Republic, belonging to the institution), Jana ZÍDKOVÁ (203 Czech Republic), Samuel LIETAVA (703 Slovakia, belonging to the institution), Jiří PACHERNÍK (203 Czech Republic) and Tomáš NOVOTNÝ (203 Czech Republic, belonging to the institution)

Edition

48th Meeting of the European Working Group on Cardiac Cellular Electrophysiology, 2024

Other information

Language

English

Type of outcome

Konferenční abstrakt

Field of Study

30201 Cardiac and Cardiovascular systems

Country of publisher

Austria

Confidentiality degree

není předmětem státního či obchodního tajemství

Organization unit

Faculty of Medicine

Keywords in English

idiopathic ventricular fibrillation; hERG; genetic variant; patch clamp

Abstract

V originále

Introduction: Variants in the cardiac ionic channel genes, including the hERG gene encoding -subunit of rapid delayed rectifier, can be identified in patients suffering from idiopathic ventricular fibrillation (iVF). A complex analysis is needed to consider the pathogenic character of an identified variant. Purpose: This study revealed 1 (out of 25) probands suffering from iVF and carrying even two hERG variants. Clinical and genetic characteristics of the proband and channel dysfunction are being examined. Methods: Clinical and genetic investigation was followed by electrophysiological experiments using whole-cell patch clamp technique at 37°C on Chinese hamster ovary cells transiently expressing human hERG channels, wild type (WT) and carrying S1021Qfs*98 variant. Results: The first VF episode occurred in the female proband at the age of 22. QTc interval (Fridericia) was 460 ms at rest and 420 ms during recovery after exercise. No pathology has been revealed (exercise test, Holter monitoring, echocardiography). Hence, the diagnosis of iVF was considered, defibrillator was implanted, and treatment using betaxolol wa started. Repeated episodes of VF were reported during the following years (16/7 years). Two hERG variants in trans, likely benign p.A228V and likely pathogenic p.S1021Qfs*98, were identified in the proband. The biophysical analysis performed in S1021Qfs*98 channels has not revealed any alteration in voltage- and time-dependent characteristics of the activation, deactivation, and inactivation, but the tail current was significantly decreased (by 70 % at 0 mV). Conclusions: A proband carrying two hERG variants but showing physiological QTc, thus, being diagnosed as iVF was identified and studied. Functional analysis of S1021Qfs*98 channels revealed a significantly decreased tail current with unaltered gating. The functional analysis of A228V and A228V/S1021Qfs*98 channels and analysis of channel expression/trafficking will follow.

Links

MUNI/A/1547/2023, interní kód MU

Name: Analýza (dys)funkce: od molekul k živému organismu

Investor: Masaryk University, Analysis of (dys)function: from molecules to the living organism

NU22-02-00348, research and development project

Name: Funkční hodnocení genetických variant u případů klinicky „skutečné“ idiopatické fibrilace komor: in vitro a in silico modelování s cílem odhalit arytmogenní mechanismus

Investor: Ministry of Health of the CR, Subprogram 1 - standard

Citovat

BÉBAROVÁ, Markéta, Natálie JANKOVÁ, Olga ŠVECOVÁ, Martin KRÁL, Jana ZÍDKOVÁ, Samuel LIETAVA, Jiří PACHERNÍK and Tomáš NOVOTNÝ. Idiopathic ventricular fibrillation: a role of variants in the hERG gene. In 48th Meeting of the European Working Group on Cardiac Cellular Electrophysiology. 2024.

@proceedings{2417417,
   author = {Bébarová, Markéta and Janková, Natálie and Švecová, Olga and Král, Martin and Zídková, Jana and Lietava, Samuel and Pacherník, Jiří and Novotný, Tomáš},
   booktitle = {48th Meeting of the European Working Group on Cardiac Cellular Electrophysiology},
   keywords = {idiopathic ventricular fibrillation; hERG; genetic variant; patch clamp},
   language = {eng},
   title = {Idiopathic ventricular fibrillation: a role of variants in the hERG gene},
   year = {2024}
}

TY  - CONF
ID  - 2417417
AU  - Bébarová, Markéta - Janková, Natálie - Švecová, Olga - Král, Martin - Zídková, Jana - Lietava, Samuel - Pacherník, Jiří - Novotný, Tomáš
PY  - 2024
TI  - Idiopathic ventricular fibrillation: a role of variants in the hERG gene
KW  - idiopathic ventricular fibrillation
KW  - hERG
KW  - genetic variant
KW  - patch clamp
N2  - Introduction: Variants in the cardiac ionic channel genes, including the hERG gene encoding -subunit of rapid delayed rectifier, can be identified in patients suffering from idiopathic ventricular fibrillation (iVF). A complex analysis is needed to consider the pathogenic character of an identified variant. Purpose: This study revealed 1 (out of 25) probands suffering from iVF and carrying even two hERG variants. Clinical and genetic characteristics of the proband and channel dysfunction are being examined. Methods: Clinical and genetic investigation was followed by electrophysiological experiments using whole-cell patch clamp technique at 37°C on Chinese hamster ovary cells transiently expressing human hERG channels, wild type (WT) and carrying S1021Qfs*98 variant. Results: The first VF episode occurred in the female proband at the age of 22. QTc interval (Fridericia) was 460 ms at rest and 420 ms during recovery after exercise. No pathology has been revealed (exercise test, Holter monitoring, echocardiography). Hence, the diagnosis of iVF was considered, defibrillator was implanted, and treatment using betaxolol wa started. Repeated episodes of VF were reported during the following years (16/7 years). Two hERG variants in trans, likely benign p.A228V and likely pathogenic p.S1021Qfs*98, were identified in the proband. The biophysical analysis performed in S1021Qfs*98 channels has not revealed any alteration in voltage- and time-dependent characteristics of the activation, deactivation, and inactivation, but the tail current was significantly decreased (by 70 % at 0 mV). Conclusions: A proband carrying two hERG variants but showing physiological QTc, thus, being diagnosed as iVF was identified and studied. Functional analysis of S1021Qfs*98 channels revealed a significantly decreased tail current with unaltered gating. The functional analysis of A228V and A228V/S1021Qfs*98 channels and analysis of channel expression/trafficking will follow.
ER  -

BÉBAROVÁ, Markéta, Natálie JANKOVÁ, Olga ŠVECOVÁ, Martin KRÁL, Jana ZÍDKOVÁ, Samuel LIETAVA, Jiří PACHERNÍK and Tomáš NOVOTNÝ. Idiopathic ventricular fibrillation: a role of variants in the hERG gene. In \textit{48th Meeting of the European Working Group on Cardiac Cellular Electrophysiology}. 2024.

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