Análisis genético de la subunidad alfa del canal de sodio dependiente de voltaje (SCN1A) en pacientes pediátricos con epilepsia refractaria

Introduction: Refractory epilepsy represents almost 30% of all types of epilepsy. Polymorphisms and mutations in specific genes are related with the pathophysiology and response to treatment of epilepsy, particularly in its association with ion channels. Ion channels have functions as controlling and maintaining action potentials in cell membranes, so that mutations in genes encoding these channels are factors related with the refractory epilepsy. Objective: To analyze the gene coding for the alpha subunit of the voltage-dependent sodium channel (SCN1A) in pediatric patients with refractory epilepsy, managed at the National Medical Center "20 de Noviembre". Methods: The molecular study was performed by analysis of exon 26 using end-point PCR and direct sequencing. The exon 26 was amplified in three fragments with the following primer pairs: 26a sense (AGG CTT CTG ACC ACT TTG AAC G), 26a antisense (TGT AGA TGT CAA TCA CCA CCA G), 26b sense (TGT GGG AAC CCA TGT GTT G), 26b antisense (CCA TGA ATC CCT CGA GCT TC), 26c sense (AAA TAC GCG TGC TTT GGT TC) and 26c antisense (GTT GTC GGG CAA TGA TGC AC). Results: Molecular analysis identified 5 children (4 males, 1 female) with a nonsynonymous mutation in heterozygous state in exon 26: change from GAA (normal) to GCC in codon 1826 of SCN1A, replacing the glutamic acid (E) by alanine (A). Conclusions: This study reports a non-conservative mutation which may be related to the lack of response to treatment in these patients, since the modification of the amino acid sequence can alter the physical and chemical characteristics and the three-dimensional structure of the alpha subunit of sodium channel, also altering its interaction with the beta subunit and as a consequence, possibly causing neuronal hyperexcitability. In Mexico do not know the prevalence of this mutation, however our invite hhalazgos confirm whether this genetic change is associated with refractory epilepsy. In Mexico do not know the prevalence of this mutation, however our findings warrant the confirmation whether this genetic change is associated with refractory epilepsy.