Mutations in the X-Linked Cyclin-Dependent Kinase–Like 5 (CDKL5/STK9

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• 作者：Jiong Tao ; Hilde Van Esch ; M. Hagedorn-Greiwe ; Kirsten Hoffmann ; Bettina Moser ; Martine Raynaud ; Jü ; rgen Sperner ; Jean-Pierre Fryns ; Eberhard Schwinger ; Jozef Gé ; cz ; Hans-Hilger Ropers ; Vera M. Kalscheuer
• 刊名：The American Journal of Human Genetics
• 出版年：2004
• 出版时间：December 2004
• 年：2004
• 卷：75
• 期：6
• 页码：1149-1154
• 全文大小：1455 K

文摘

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.