AUTHOR=Liu Xianyu , Shen Qiyang , Zheng Guo , Guo Hu , Lu Xiaopeng , Wang Xiaoyu , Yang Xiao , Cao Zixuan , Chen Jing 

TITLE=Gene and Phenotype Expansion of Unexplained Early Infantile Epileptic Encephalopathy

JOURNAL=Frontiers in Neurology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.633637

DOI=10.3389/fneur.2021.633637

ISSN=1664-2295

ABSTRACT=<p><bold>Objective:</bold> The genetic aetiology of epileptic encephalopathy (EE) is growing rapidly based on next generation sequencing (NGS) results. In this single-centre study, we aimed to investigate a cohort of Chinese children with early infantile epileptic encephalopathy (EIEE).</p><p><bold>Methods:</bold> NGS was performed on 50 children with unexplained EIEE. The clinical profiles of children with pathogenic variants were characterised and analysed in detail. Conservation analysis and homology modelling were performed to predict the impact of <italic>STXBP1</italic> variant on the protein structure.</p><p><bold>Results:</bold> Pathogenic variants were identified in 17 (34%) of 50 children. Sixteen variants including <italic>STXBP1</italic> (<italic>n</italic> = 2), <italic>CDKL5</italic> (<italic>n</italic> = 2), <italic>PAFAH1B1, SCN1A</italic> (<italic>n</italic> = 9), <italic>SCN2A</italic>, and <italic>KCNQ2</italic> were <italic>de novo</italic>, and one (<italic>PIGN</italic>) was a compound heterozygous variant. The phenotypes of the identified genes were broadened. <italic>PIGN</italic> phenotypic spectrum may include EIEE. The <italic>STXBP1</italic> variants were predicted to affect protein stability.</p><p><bold>Significance:</bold> NGS is a useful diagnostic tool for EIEE and contributes to expanding the EIEE-associated genotypes. Early diagnosis may lead to precise therapeutic interventions and can improve the developmental outcome.</p>