Publication details
Funkční analýza varianty M135V v genu SCN5A asociované s idiopatickou komorovou fibrilací
| Title in English | Functional analysis of the M135V variant in the SCN5A gene associated with idiopathic ventricular fibrillation |
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| Authors | |
| Year of publication | 2026 |
| Type | Conference abstract |
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| Citation | |
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| Description | Variants in cardiac ion channel genes , including the SCN5A gene encoding the ?-subunit of the cardiac sodium channel Nav1.5, can be identified in patients with idiopathic ventricular fibrillation (iVF). Many of these variants are classified as variants of uncertain significance (VUS). Analysis of dysfunction of the targeted channel is thus essential to assess their pathogenic potential. In this study we examined the pathogenic potential of a novel variant (M135V) in the SCN5A gene identified in a patient with iVF. Our approach combined clinical, genetic, and functional analysis of this variant. Electrophysiological properties were assessed using the whole-cell patch-clamp technique at 23 °C in Chinese Hamster Ovary (CHO) cells expressing wild-type (WT), M135V, or heterozygous (WT/M135V) channels coexpressed with the WT ß1-subunit (ratio 1:1). The proband was a 40-year-old female diagnosed with iVF after an episode of ventricular fibrillation (no significant cardiac findings, including ECG and echocardiography). Genetic testing revealed a VUS variant M135V in the SCN5A gene of the proband and her asymptomatic father. Peripheral blood samples were collected for the preparation of patient-specific cardiomyocytes of the proband (WT/M135V), her father (WT/M135V), and healthy brother (WT/WT). Functional analysis of the variant using CHO cells is currently performed. Electrophysiological properties of the WT channel were consistent with previously published data (half activation/inactivation voltage V1/2 = –23.9 / –72.6 mV, slope factor k = 8.64 / –5.89, fast and slow time constant of recovery from inactivation ?rec,f and ?rec,s = 8.40 ms and 128.9 ms at –100 mV, 34.9 ms and 297.1 ms at –80 mV). Electrophysiological properties of the M135V variant and heterozygous WT/M135V channels did not significantly differ from WT channels. The only significant change was observed in ?rec,f at –80 mV, which was faster in M135V and WT/M135V than in WT (19.7 ms for M135V and 23.2 ms for WT/M135V, vs. 34.9 ms for WT). Current analysis of the M135V variant did not show major alterations in the electrophysiological properties of the sodium channel. Future studies using patient-specific induced pluripotent stem cell-derived cardiomyocytes will further assess the pathogenic potential of the variant. |
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