Department of Molecular Biology and Genetics, Genome Centre, Biruni University, Zeytinburnu, Istanbul, Turkey.
İstinye University Faculty of Medicine, Maltepe, Zeytinburnu, İstanbul, Turkey.
Acta Biochim Pol. 2020 Sep 15;67(3):431-434. doi: 10.18388/abp.2020_5364.
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.
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.
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.
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.
早发性婴儿癫痫性脑病 57 型属于一组脑病，其特征为早期发病、严重脑电图异常、癫痫发作、发育迟缓及智力残疾。
我们使用下一代测序（NGS）进行全外显子分析，并进行生物信息学分析，以寻找与患者表型相关的突变。通过 PolyPhen2 和 Swissmodel ExPASy 分析突变对蛋白质结构的影响。
在这项研究中，我们评估了两名被诊断为 EIEE 57 型的土耳其男性，以调查该疾病的遗传原因。全外显子组测序显示 KCN2 基因突变，该基因是与癫痫性脑病相关的钾通道（KCN）基因家族的成员。此处报道了两种突变，c.545A>T（p.Asn182Ile 和 c.2638C>A（p.Leu880Met），这是一种新的突变。
我们的发现提示这些突变与基因型-表型的相关性。此外，计算分析表明它们对蛋白质结合位点和功能的影响，提示它们在早发性婴儿癫痫性脑病 57 的发病机制中的作用。
