Tao Jiong, Van Esch Hilde, Hagedorn-Greiwe M, Hoffmann Kirsten, Moser Bettina, Raynaud Martine, Sperner Jürgen, Fryns Jean-Pierre, Schwinger Eberhard, Gécz Jozef, Ropers Hans-Hilger, Kalscheuer Vera M
Max-Planck-Institute for Molecular Genetics, Berlin, Germany.
Am J Hum Genet. 2004 Dec;75(6):1149-54. doi: 10.1086/426460.
Recently, we showed that truncation of the X-linked cyclin-dependent kinase-like 5 (CDKL5/STK9) gene caused mental retardation and severe neurological symptoms in two female patients. Here, we report that de novo missense mutations in CDKL5 are associated with a severe phenotype of early-onset infantile spasms and clinical features that overlap those of other neurodevelopmental disorders, such as Rett syndrome and Angelman syndrome. The mutations are located within the protein kinase domain and affect highly conserved amino acids; this strongly suggests that impaired CDKL5 catalytic activity plays an important role in the pathogenesis of this neurodevelopmental disorder. In view of the overlapping phenotypic spectrum of CDKL5 and MECP2 mutations, it is tempting to speculate that these two genes play a role in a common pathogenic process.
最近，我们发现X连锁的细胞周期蛋白依赖性激酶样5（CDKL5/STK9）基因的截短在两名女性患者中导致智力迟钝和严重的神经症状。在此，我们报告CDKL5的新生错义突变与早发性婴儿痉挛的严重表型以及与其他神经发育障碍（如雷特综合征和天使综合征）重叠的临床特征相关。这些突变位于蛋白激酶结构域内，影响高度保守的氨基酸；这强烈表明CDKL5催化活性受损在这种神经发育障碍的发病机制中起重要作用。鉴于CDKL5和MECP2突变的表型谱重叠，很容易推测这两个基因在共同的致病过程中起作用。
