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

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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.

LanguageEnglish
Pages1149-1154
Number of pages6
JournalAmerican Journal of Human Genetics
Volume75
Issue number6
DOIs
Publication statusPublished - 1 Jan 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
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. / Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5/STK9) gene are associated with severe neurodevelopmental retardation. In: American Journal of Human Genetics. 2004 ; Vol. 75, No. 6. pp. 1149-1154.
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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.",
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Tao, J, Van Esch, H, Hagedorn-Greiwe, M, Hoffmann, K, Moser, B, Raynaud, M, Sperner, J, Fryns, JP, Schwinger, E, Gécz, J, Ropers, HH & Kalscheuer, VM 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, vol. 75, no. 6, pp. 1149-1154. https://doi.org/10.1086/426460

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

In: American Journal of Human Genetics, Vol. 75, No. 6, 01.01.2004, p. 1149-1154.

Research output: Contribution to journalArticle

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AU - Tao, Jiong

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AU - Hagedorn-Greiwe, M.

AU - Hoffmann, Kirsten

AU - Moser, Bettina

AU - Raynaud, Martine

AU - Sperner, Jürgen

AU - Fryns, Jean Pierre

AU - Schwinger, Eberhard

AU - Gécz, Jozef

AU - Ropers, Hans Hilger

AU - Kalscheuer, Vera M.

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