Phenotypic manifestations of Val93Ile missense mutation and its influence on Kir2.1 channel functioning

A patient with asymptomatic QT interval prolongation was found to have missense mutation c.277G>A (p.Val93Ile) in the KCNJ2 gene, previously described in the literature as the cause of a familial form of atrial fibrillation only. The corresponding amino acid substitution was introduced into the plasmid encoding the Kir2.1 channel and the mutant gene was expressed in Chinese hamster ovary cells (CHO-K1) to evaluate the effect of the mutation on IK1 current parameters. Using the whole-cell patch-clamp technique in the potential fixation mode, the integral current of IK1 was studied. As a result of the study, it was shown that the c.277G>A (p. Val93Ile) mutation is implemented according to the “gain of function” type and significantly changes the functioning of Kir 2.1 channel. The presence of a stable activating effect on protein function argues in favor of the clinical significance of the identified variant.

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