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Hum Mutat. 2019 Mar;40(3):281-287. doi: 10.1002/humu.23690. Epub 2018 Dec 8.

A de novo pathogenic CSNK1E mutation identified by exome sequencing in family trios with epileptic encephalopathy.

Chen X1,2, Jin J1,3, Wang Q1,4, Xue H1,3, Zhang N1, Du Y1,5, Zhang T1, Zhang B1, Wu J1, Liu Z1.

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Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, China.
Center of Scientific Research, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.
Department of Laboratory Medicine, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Research Center of Blood Transfusion Medicine, Education Ministry Key Laboratory of Laboratory Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.


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.


CSNK1E; STXBP1; de novo mutations; epileptic encephalopathy; whole-exome sequencing


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