2024
Idiopathic ventricular fibrillation: a role of variants in the hERG gene
BÉBAROVÁ, Markéta, Natálie JANKOVÁ, Olga ŠVECOVÁ, Martin KRÁL, Jana ZÍDKOVÁ et. al.Základní údaje
Originální název
Idiopathic ventricular fibrillation: a role of variants in the hERG gene
Autoři
BÉBAROVÁ, Markéta (203 Česká republika, garant, domácí), Natálie JANKOVÁ (203 Česká republika, domácí), Olga ŠVECOVÁ (203 Česká republika, domácí), Martin KRÁL (203 Česká republika, domácí), Jana ZÍDKOVÁ (203 Česká republika), Samuel LIETAVA (703 Slovensko, domácí), Jiří PACHERNÍK (203 Česká republika) a Tomáš NOVOTNÝ (203 Česká republika, domácí)
Vydání
48th Meeting of the European Working Group on Cardiac Cellular Electrophysiology, 2024
Další údaje
Jazyk
angličtina
Typ výsledku
Konferenční abstrakt
Obor
30201 Cardiac and Cardiovascular systems
Stát vydavatele
Rakousko
Utajení
není předmětem státního či obchodního tajemství
Organizační jednotka
Lékařská fakulta
Klíčová slova anglicky
idiopathic ventricular fibrillation; hERG; genetic variant; patch clamp
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 19. 8. 2024 14:15, Mgr. Tereza Miškechová
Anotace
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.
Návaznosti
| MUNI/A/1547/2023, interní kód MU |
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| NU22-02-00348, projekt VaV |
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