PDF(Pubmed)
Abstract：
Pathogenic variants in CHD2 have been reported to have a wide range of phenotypic variability in neurodevelopmental disorders, such as early-onset epileptic encephalopathy, developmental delay, and behavior problems. So far, there is no clear correlation between genotypes and phenotypes. This study reports a Chinese patient with a novel heterozygous CHD2 mutation (c.4318C>T, pArg1440*). Her main clinical manifestations include developmental delay, myoclonic epilepsy, and hypothyroidism. Then, we reviewed a total of 144 individuals carrying CHD2 variants with epileptic encephalopathy. In terms of clinical manifestations, these patients are usually described with variable epilepsy phenotypes, including idiopathic photosensitive occipital epilepsy, Dravet syndrome, Jeavons syndrome, Lennox-Gastaut syndrome, juvenile myoclonic epilepsy, and non-specific epileptic encephalopathy. Among them, myoclonic seizures and generalized tonic-clonic seizures are the main seizure types in all patients hosting CHD2 single-nucleotide or indel variants (non-CNVs). At the molecular level, there are 102 types of CHD2 non-CNVs in 126 patients, almost one mutational type corresponding to one person, and there is no difference in the incidence ratio of each position. Furthermore, we summarized that a small proportion of patients inherited CHD2 variants, and not all patients with CHD2 variants had seizures. Importantly, the phenotypes, especially seizures control and fever sensitivity, and genotypes had a relative association. These results enriched the database of CHD2-relative neurodevelopmental disorders and provided a theoretical foundation for researching the relationship between genotypes and phenotypes.
摘要：
据报道，CHD2中的致病变体在神经发育障碍中具有广泛的表型变异性，比如早发性癫痫性脑病，发育迟缓,和行为问题。到目前为止,基因型和表型之间没有明显的相关性。本研究报告了一名中国患者，该患者具有新的杂合CHD2突变（c.4318C>T，pArg1440*).她的主要临床表现包括发育迟缓，肌阵挛性癫痫,和甲状腺功能减退。然后，我们共回顾了144例CHD2变异体伴癫痫性脑病患者.在临床表现方面，这些患者通常被描述为具有可变的癫痫表型，包括特发性光敏性枕叶癫痫,德拉韦综合征,Jeavons综合征,Lennox-Gastaut综合征,青少年肌阵挛性癫痫，和非特异性癫痫性脑病。其中,肌阵挛性发作和全身性强直-阵挛性发作是所有CHD2单核苷酸或indel变异(非CNVs)患者的主要发作类型.在分子水平上,126例患者中有102种CHD2非CNV，几乎一个突变类型对应于一个人，每个位置的发病率没有差异。此外，我们总结了一小部分患者遗传CHD2变异，并非所有CHD2变异的患者都有癫痫发作.重要的是,表型，尤其是癫痫发作控制和发热敏感性，和基因型有相对关联。这些结果丰富了CHD2相关神经发育障碍的数据库，为研究基因型与表型之间的关系提供了理论基础。
