The cyclin-dependent kinase like 5 (CDKL5) gene variation is X-linked dominant and is associated with type 2 developmental and epileptic encephalopathy (DEE). Although numerous cases of CDKL5 have been reported, there is limited discussion regarding functional verification. We described two children with DEE caused by de novo variations of CDKL5 gene, analyzed their clinical manifestations, and performed genetic testing on their gene variation sites. The two cases presented with tonic seizures followed by epileptic spasms, indicative of refractory epilepsy. Physical examination revealed abnormal facial features, including wide eye distance, low nose base, and high nose bridge. Both cases exhibited developmental disabilities. Cranial magnetic resonance imaging (MRI) showed widening of the bilateral frontotemporal extracerebral space. Genetic testing identified variations at the gene sites c.463 + 4A > G (splicing) and c.1854_1861delCAAAGTGA (p.D618Efs*18). Minigene experiments further confirmed that the intronic variation c.463 + 4A > G (splicing) disrupted splicing, leading to protein truncation. CDKL5 gene variation can lead to DEE, and intron variation site c.463 + 4A > G (splicing) can cause protein truncation, which is a pathogenic variation.

细胞周期蛋白依赖性激酶样 5 (CDKL5) 基因变异为 X 连锁显性变异，与 2 型发育性脑病和癫痫性脑病 (DEE) 相关。尽管已经报道了许多 CDKL5 病例，但有关功能验证的讨论却很有限。我们描述了两名由CDKL5基因新生变异引起的DEE儿童，分析了他们的临床表现，并对他们的基因变异位点进行了基因检测。两例患者均出现强直性癫痫发作，随后出现癫痫性痉挛，提示为难治性癫痫。体检发现面部特征异常，包括宽眼距、低鼻基、高鼻梁。两个病例都表现出发育障碍。头颅磁共振成像（MRI）显示双侧额颞叶脑外间隙增宽。基因测试发现了基因位点 c.463 + 4A > G（剪接）和 c.1854_1861delCAAAGTGA (p.D618Efs*18) 的变异。小基因实验进一步证实，内含子变异c.463 + 4A > G（剪接）破坏了剪接，导致蛋白质截短。CDKL5基因变异可导致DEE，内含子变异位点c.463+4A>G（剪接）可引起蛋白质截短，这是一种致病性变异。