| Description |
Objectives: In some patients suffering from idiopathic ventricular fibrillation (VF), variants in genes encoding cardiac ionic channels may be identified. A complex analysis has to be used to consider the possible pathogenic character of the identified variant. This study is focused on clinical, genetic, and functional analysis of a proband suffering from idiopathic VF and carrying two variants in the hERG (KCNH2) gene. Methods: After clinical and genetic investigation of the proband and family members, we have recently started electrophysiological analysis using whole-cell patch clamp technique at 37°C on Chinese hamster ovary cells transiently expressing human hERG channels, both wild type (WT) and carrying S1021Qfs*98 variant. Results: The proband, a female, was diagnosed at the age of 22 when she experienced her first attack of VF and was successfully resuscitated. QT interval corrected to the heart rate by the Bazett formula (QTc,B) and Fridericia formula (QTc,F) were 460 ms at rest. Qtc,B and QTc,F were 480 and 400 ms, respectively, during the exercise test and 460 and 420 ms, respectively, during the following recovery. No arrhythmia was detected during the exercise test as well as Holter monitoring. Echocardiography did not reveal any pathology as well. Hence, she was diagnosed as idiopathic VF, ICD was implanted, and she was treated using betaxolol. Repeated episodes of VF were reported during the following years (16 episodes per 7 years). Two hERG variants in trans, p. A228V and p.S1021Qfs*98, were identified in the proband, thus, functional analysis has been started. We have not identified any clear deviation in activation and deactivation of S1021Qfs*98 channels, but the tail current was significantly decreased by about 70 % in S1021Qfs*98 channels vs. WT channels. Currently, analysis of the channel inactivation proceeds. Conclusions: A proband suffering from idiopathic VF and carrying two hERG variants was identified and studied. Functional analysis of S1021Qfs*98 channels revealed a significantly decreased tail current with unaltered activation and deactivation gating. The functional analysis of A228V and co-expressed A228V/S1021Qfs*98 channels as well as analysis of channel expression and trafficking will follow.
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