Diebold Bertrand, Delépine Chloé, Gataullina Svetlana, Delahaye Andrée, Nectoux Juliette, Bienvenu Thierry
Laboratoire de Biochimie et Génétique Moléculaire, Hôpital Cochin, Assistance Publique - Hôpitaux de Paris, Paris, France.
1] Inserm, U1016, Paris, France [2] Institut Cochin, Université Paris Descartes, Sorbonne Paris Cité, CNRS (UMR 8104), Paris, France.
Eur J Hum Genet. 2014 Feb;22(2):270-2. doi: 10.1038/ejhg.2013.133. Epub 2013 Jun 12.
Mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene have been described in girls with Rett-like features and early-onset epileptic encephalopathy including infantile spasms. Milder phenotypes have been associated with sequence variations in the 3'-end of the CDKL5 gene. Identification of novel CDKL5 transcripts coding isoforms characterized by an altered C-terminal region strongly questions the eventual pathogenicity of sequence variations located in the 3'-end of the gene. We investigated a group of 30 female patients with a clinically heterogeneous phenotype ranging from nonspecific intellectual disability to a severe neonatal encephalopathy and identified two heterozygous CDKL5 missense mutations, the previously reported p.Val999Met and the novel mutation p.Pro944Thr. However, these mutations have also been detected in their healthy father. Considering our results and all data from the literature, we suggest that genetic variations beyond the codon 938 in human CDKL5115 protein may have minor or no significance. It is probable that screening of exons 19-21 of the CDKL5 gene is not useful in practical molecular diagnosis of atypical Rett syndrome.
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（CDKL5）基因突变。较轻的表型与CDKL5基因3'端的序列变异有关。鉴定编码具有改变的C末端区域的异构体的新型CDKL5转录本，强烈质疑位于该基因3'端的序列变异的最终致病性。我们调查了一组30名女性患者，她们的临床表型各异，从非特异性智力残疾到严重的新生儿脑病，并鉴定出两个杂合的CDKL5错义突变，即先前报道的p.Val999Met和新突变p.Pro944Thr。然而，在她们健康的父亲中也检测到了这些突变。考虑到我们的结果以及文献中的所有数据，我们认为人类CDKL5115蛋白中密码子938以外的基因变异可能意义不大或没有意义。对CDKL5基因第19 - 21外显子进行筛查，在非典型雷特综合征的实际分子诊断中可能并无用处。
