Title : De novo mutations of SCN1A and KCNT1 genes at patients with channelopathy forms of epilepsy from kazakhstan
Epilepsy is one of the most common and heterogeneous neurological diseases. In Kazakhstan, more than 45,000 people suffer from epilepsy, 40% of them are children, adolescents and young people, 38% of patients become disabled, and their life quality reduces by 85% on average. The main perspectives in reducing such high rates of morbidity and mortality associate with the improvement of diagnostic methods that have scientifically based effectiveness. Both hereditary and environmentally acquired factors are involved in epilepsy pathogenesis. The molecular mechanisms underlying the various epileptic seizures have been intensively studied for more than two decades. The genetic impact plays a big role in the etiology of epilepsy idiopathic forms. Recent data indicate that remaining 70-80% of cases development due to genetic background. Most of the epilepsy hereditary forms with established gene mutations are caused by the damage of ion channels that ensure the neuronal membrane polarization. Such epilepsy forms are referred to the channelopathy group. First of all, they include the genes of sodium, potassium, calcium and chloride channels.
The purpose of our research is to determine the spectrum of cause-effect mutations in SCN1A and KCNT1 genes at patients suffered from channelopathy forms of epilepsy. Mutations in the sodium channel gene SCN1A were described for 70% of children suffering from Dravet syndrome, most of the mutations had spontaneous nature. SCN1A mutations can cause the development of severe myoclonic epilepsy in infancy (SMEI) and borderline (SMEB), which related to symptomatic forms. The dominant mutations in the KCNT1, sodium-potassium channel gene intensely expressed in the brain, cause autosomal dominant night frontal lobe epilepsy (ADNFLE), malignant migrating partial seizures of infancy (MMPSI), and temporal lobe epilepsy (TLE). Mutations in this gene increase the membrane permeability that leads to unregulated excitation of neurons in the brain.