New mutations in KCNT2 gene causing early infantile epileptic encephalopathy type 57: Case study and literature review

Meryem Alagoz; Nasim Kherad; Sureyya  Bozkurt; Adnan Yuksel

doi:10.18388/abp.2020_5364

Meryem Alagoz Department of Molecular Biology and Genetics, Genome Centre, Biruni University, Zeytinburnu, Istanbul, Turkey https://orcid.org/0000-0002-6243-2146
Nasim Kherad Department of Molecular Biology and Genetics, Genome Centre, Biruni University, Zeytinburnu, Istanbul, Turkey https://orcid.org/0000-0003-0884-2803
Sureyya Bozkurt İstinye University Faculty of Medicine, Maltepe, Zeytinburnu, İstanbul, Turkey https://orcid.org/0000-0002-1765-9894
Adnan Yuksel Department of Molecular Biology and Genetics, Genome Centre, Biruni University, Zeytinburnu, Istanbul, Turkey

DOI: https://doi.org/10.18388/abp.2020_5364

Abstract

Purpose. Early infantile epileptic encephalopathy (EIEE) 57 belongs to a group of encephalopathies with early-onset and characterised by severe electroencephalogram abnormalities, seizures, developmental delay and intellectual disability. Method. We carried out Whole Exome analysis using Next Generation Sequencing (NGS) and bioinformatic analysis performed to find mutation associated with the patient phenotypes. The effect of the mutation on protein structure analysed by PolyPhen2 and Swissmodel ExPASy. Results. In this study, we evaluated two unrelated Turkish males diagnosed with EIEE type 57 to investigate the genetic cause of this disease. Whole exome sequencing revealed mutations in KCN2 gene, which is a member of Potassium channels (KCN) gene family associated with epileptic encephalopathies. Two mutations, c.545A>T (p.Asn182Ile and c.2638C>A (p.Leu880Met) were reported here as a novel mutation. Conclusions. Our findings implicate the genotype-phenotype correlation of these mutations. Furthermore, the computational analysis showed their effect on protein binding site and function suggesting their role in the development of early infantile epileptic encephalopathy 57.