Bahi-Buisson N, Bienvenu T
Inserm, Université Paris Descartes, Paris, France.
Mol Syndromol. 2012 Apr;2(3-5):137-152. doi: 10.1159/000331333. Epub 2011 Sep 13.
Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) have been described in girls with Rett-like features and early-onset epileptic encephalopathy including infantile spasms. To date, with more than 80 reported cases, the phenotype of CDKL5-related encephalopathy is better defined. The main features consist of early-onset seizures starting before 5 months of age, severe mental retardation with absent speech and Rett-like features such as hand stereotypies and deceleration of head growth. On the other hand, neuro-vegetative signs and developmental regression are rare in CDKL5 mutation patients. The CDKL5 gene encodes a serine threonine kinase protein which is characterized by a catalytic domain and a long C-terminal extension involved in the regulation of the catalytic activity of CDKL5 and in the sub-nuclear localization of the protein. To our knowledge, more than 70 different point mutations have been described including missense mutations within the catalytic domain, nonsense mutations causing the premature termination of the protein distributed in the entire open reading frame, splice variants, and frameshift mutations. Additionally, CDKL5 mutations have recently been described in 7 males with a more severe epileptic encephalopathy and a worse outcome compared to female patients. Finally, about 23 male and female patients have been identified with gross rearrangements encompassing all or part of the CDKL5 gene, with a phenotype reminiscent of CDKL5-related encephalopathy combined with dysmorphic features. Even if recent data clearly indicate that CDKL5 plays an important role in brain function, the protein remains largely uncharacterized. Phenotype-genotype correlation is additionally hampered by the relatively small number of patients described.
在具有雷特氏症样特征和早发性癫痫性脑病（包括婴儿痉挛症）的女孩中，已发现细胞周期蛋白依赖性激酶样5基因（CDKL5）发生突变。迄今为止，已有80多例报告病例，CDKL5相关脑病的表型得到了更明确的定义。其主要特征包括5个月前开始的早发性癫痫发作、严重智力迟钝且无语言能力以及雷特氏症样特征，如手部刻板动作和头围增长减速。另一方面，CDKL5突变患者很少出现神经植物体征和发育倒退。CDKL5基因编码一种丝氨酸苏氨酸激酶蛋白，其特征在于一个催化结构域和一个长的C末端延伸区，该延伸区参与CDKL5催化活性的调节以及该蛋白的核内定位。据我们所知，已描述了70多种不同的点突变，包括催化结构域内的错义突变、导致蛋白质过早终止的无义突变（分布在整个开放阅读框中）、剪接变体和移码突变。此外，最近在7名男性中发现了CDKL5突变，他们患有比女性患者更严重的癫痫性脑病且预后更差。最后，已确定约23名男性和女性患者存在涵盖全部或部分CDKL5基因的大片段重排，其表型让人联想到CDKL5相关脑病并伴有畸形特征。即使最近的数据清楚地表明CDKL5在脑功能中起重要作用，但该蛋白在很大程度上仍未得到充分表征。此外，由于所描述的患者数量相对较少，表型 - 基因型相关性研究也受到了阻碍。
