Department of Physiology and Medical Physics, RCSI, University of Medicine and Health Sciences, Dublin 02, Ireland.
FutureNeuro SFI Research Centre, RCSI, University of Medicine and Health Sciences, Dublin D02 YN77, Ireland.
Int J Mol Sci. 2021 Jan 8;22(2):588. doi: 10.3390/ijms22020588.
Epileptic encephalopathies (EE) are severe epilepsy syndromes characterized by multiple seizure types, developmental delay and even regression. This class of disorders are increasingly being identified as resulting from de novo genetic mutations including many identified mutations in the family of chromodomain helicase DNA binding (CHD) proteins. In particular, several de novo pathogenic mutations have been identified in the gene encoding chromodomain helicase DNA binding protein 2 (CHD2), a member of the sucrose nonfermenting (SNF-2) protein family of epigenetic regulators. These mutations in the CHD2 gene are causative of early onset epileptic encephalopathy, abnormal brain function, and intellectual disability. Our understanding of the mechanisms by which modification or loss of CHD2 cause this condition remains poorly understood. Here, we review what is known and still to be elucidated as regards the structure and function of CHD2 and how its dysregulation leads to a highly variable range of phenotypic presentations.
癫痫性脑病 (EE) 是一种严重的癫痫综合征，其特征为多种发作类型、发育迟缓甚至倒退。这一类疾病越来越多地被确定为由新生基因突变引起，包括染色质解旋酶 DNA 结合 (CHD) 蛋白家族中的许多已鉴定突变。特别是，在编码染色质解旋酶 DNA 结合蛋白 2 (CHD2) 的基因中发现了几个新生致病性突变，CHD2 是表观遗传调节剂蔗糖非发酵 (SNF-2) 蛋白家族的成员。CHD2 基因中的这些突变是导致早发性癫痫性脑病、脑功能异常和智力障碍的原因。我们对 CHD2 发生改变或缺失导致这种情况的机制仍知之甚少。在这里，我们回顾了关于 CHD2 的结构和功能以及其失调如何导致高度可变的表型表现的已知和仍有待阐明的内容。
