Recent whole‐exome sequencing (WES) studies have demonstrated the contribution of de novo mutations (DNMs) to epileptic encephalopathies (EEs). Here, we performed WES on four trios with West syndrome and identified three loss‐of‐function DNMs in...
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https://www.riss.kr/link?id=O119302074
Xiaomin Chen ; Jing Jin ; Qiongdan Wang ; Huangqi Xue ; Na Zhang ; Yaoqiang Du ; Tao Zhang ; Bing Zhang ; Jinyu Wu ; Zhenwei Liu
2019년
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1059-7794
1098-1004
SCI;SCIE;SCOPUS
학술저널
281-287 [※수록면이 p5 이하이면, Review, Columns, Editor's Note, Abstract 등일 경우가 있습니다.]
0
상세조회0
다운로드다국어 초록 (Multilingual Abstract)
Recent whole‐exome sequencing (WES) studies have demonstrated the contribution of de novo mutations (DNMs) to epileptic encephalopathies (EEs). Here, we performed WES on four trios with West syndrome and identified three loss‐of‐function DNMs in...
Recent whole‐exome sequencing (WES) studies have demonstrated the contribution of de novo mutations (DNMs) to epileptic encephalopathies (EEs). Here, we performed WES on four trios with West syndrome and identified three loss‐of‐function DNMs in both CSNK1E (c.885+1G>A) and STXBP1 (splicing, c.1111‐2A>G; nonsense, p.(Y519X)). The splicing mutation in CSNK1E creates insertion of 116 new amino acids at position 246 followed by a premature stop codon. Both CSNK1E and STXBP1 showed a closer coexpression relationship with epilepsy candidate genes beyond that expected by chance. In addition, genes coexpressed with CSNK1E were enriched in early prenatal stages across multiple brain regions. We also found that 60 CSNK1E‐interacting genes share an association with multiple neuropsychiatric disorders, and these genes formed a significant interconnected interaction network with roles in the midbrain development. Our study supported the potential role of CSNK1E variants in EE susceptibility and expanded the phenotypic spectrum associated with CSNK1E variation.
We identified three loss‐of‐function de novo mutations in both CSNK1E (c.885+1G>A) and STXBP1 (splicing, c.1111‐2A>G; nonsense, p.(Y519X)) from four trios with epileptic encephalopathies (EEs) using whole‐exome sequencing. The splicing mutation in CSNK1E creates insertion of 116 new amino acids at position 246 followed by a premature stop codon and cause the break of protein kinase domain. Through multiple bioinformatics analyses, our study presented genetic evidence supporting the potential role of CSNK1E variants in the pathogenesis of EEs.
Cover Image, Volume 40, Issue 3