Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5/STK9) gene are associated with severe neurodevelopmental retardation

Jiong Tao, Hilde Van Esch, M. Hagedorn-Greiwe, Kirsten Hoffmann, Bettina Moser, Martine Raynaud, Jürgen Sperner, Jean Pierre Fryns, Eberhard Schwinger, Jozef Gécz, Hans Hilger Ropers, Vera M. Kalscheuer

Research output: Contribution to journalArticle

223 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1149-1154
Number of pages6
JournalAmerican Journal of Human Genetics
Volume75
Issue number6
DOIs
Publication statusPublished - Dec 2004
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Tao, J., Van Esch, H., Hagedorn-Greiwe, M., Hoffmann, K., Moser, B., Raynaud, M., ... Kalscheuer, V. M. (2004). Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5/STK9) gene are associated with severe neurodevelopmental retardation. American Journal of Human Genetics, 75(6), 1149-1154. https://doi.org/10.1086/426460