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

Am J Hum Genet 2004 Dec;75(6):1149-54

Max-Planck-Institute for Molecular Genetics, Berlin, Germany.

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.

Download full-text PDF

Source
http://linkinghub.elsevier.com/retrieve/pii/S000292970760084
Publisher Site
http://dx.doi.org/10.1086/426460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182152PMC
December 2004
2 Reads

Publication Analysis

Top Keywords

kinase-like cdkl5/stk9
8
cdkl5/stk9 gene
8
cyclin-dependent kinase-like
8
associated severe
8
x-linked cyclin-dependent
8
domain affect
4
kinase domain
4
located protein
4
affect highly
4
protein kinase
4
conserved amino
4
suggests impaired
4
acids suggests
4
amino acids
4
mutations located
4
highly conserved
4
angelman syndrome
4
infantile spasms
4
overlap neurodevelopmental
4
spasms clinical
4

Similar Publications