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=Volume 12 - 2021

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=Objective: The genetic etiology of epileptic encephalopathy (EE) is growing rapidly
by next generation sequencing (NGS) technique. In this single-center study, we aimed
to investigate a cohort of Chinese children with early infantile epileptic encephalopathy
(EIEE).
Methods: NGS was performed on 50 children with unexplained EIEE. The clinical
profiles of children with pathogenic variants were characterized and analysed in detail.
The conservation analysis and homology modelling were to predict the impact of
STXBP1 mutation on the protein structure.
Results: Pathogenic variants were identified in 17 (34%) out of 50 children. Sixteen
variants were de novo, and one was a compound heterozygous mutation. Gene and
phenotype were broadened, and PIGN as a new candidate EIEE gene needed further
functional study. The molecular mechanism of STXBP1 mutation revealed the alteration
of amino acid affected the protein stability.
Significance: NGS is a useful diagnostic tool, and single genes with causative de novo
variants or compound heterozygous are discovered to allow for expansion of gene and
phenotype in EIEE. Early recognition could lead to early diagnosis and gene
intervention to offer an improved developmental outcome.