Problemas neurológicos

Two Distinct De novo Pathogenic Sequence Variants in the SCN2A Gene in Children with Early Infantile Epileptic Encephalopathy/Ohtahara Syndrome

Abstract

Marketa Wayhelova, Jan Oppelt, Jan Smetana, Hana Filkova, Eva Hladilkova, Jana Soukalova, Renata Gaillyova and Petr Kuglik

Early infantile epileptic encephalopathy/Ohtahara syndrome represents a group of genetically heterogeneous disorders affecting normal brain development and functioning. In this work, we present a case of two unrelated children diagnosed with early infantile epileptic encephalopathy and associated multiple congenital abnormalities. To obtain genetic diagnosis, these children were examined through multi-step diagnostic algorithm including G-banded karyotype analysis and whole-genomic screening using array-based comparative genomic hybridization (array-CGH) with negative results. Additionally, these children and their unaffected parents were enrolled for our pilot study of targeted nextgeneration sequencing technology (NGS) using commercial panel ClearSeq Inherited DiseaseXT (Agilent Technologies) and consequent validation by Sanger sequencing. Our analysis detected two distinct de novo pathogenic sequence variants in the SCN2A gene, resulting in p.Met1545Val and p.Ala263Val changes on the SCN2A protein level and explaining their pathological phenotypes.

In conclusion, our findings indicate that NGS can become the optimal approach to the genetics diagnostics of disorders of central nervous system (CNS) which can lead to the discovery of new candidate genes.