Спектр мутаций в гене SCN4A у пациентов с недистрофическими миотониями

Abstract

Nondystrophic myotonias are a group of muscle channelopathies. Mutations of CLCN1 and SCN4A genes cause the dysfunction of chloric and sodium ion channels. There are chloric channel myotonias (Thomsen’s and Becker’s types) and sodium channel myotonias (paramyotonia of Eulenburg, HyperkalemicPeriodic paralysis with myotonia, Potassium-aggravated myotonia, Myotonia fluctuans). Patients need in molecular-genetic testing for a right diagnose because some forms of nondystrophic myotonias are very similar. The aim of this work is to describe the spectrum of SCN4A mutations in Russian patients with sodium channel myotonias. The SCN4A mutations were revealed in 13 patients (54%). Five of these mutations were novel: c.205G>A (p.Gly69Arg), c.638G>A (p.Gly213Asp), c.2003T>C (p.Leu668Pro), c.2017C>G (p.Leu673Val), c.4137G>C (p.Gln1379His). All mutations were missense. Mutations in the exons 12, 13 и 22 of SCN4A gene account for 77% causes of sodium channel myotonias. The SCN4A mutations were found in patients with Thomsen’s myotonia (n = 4), paramyotonia of Eulenburg (n = 3), myotonia congenita (n = 2), Hyperkalemic Periodic paralysis (n = 2), Hypokalemic Periodic paralysis (n = 2). It is expediently to make molecular genetic analysis of SCN4A gene for patients with Thomsen’s myotonia and myotonia congenita.