title: Epilepsy caused by CDKL5 mutations.
abstract: Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) have been identified in female patients with early onset epileptic encephalopathy and severe mental retardation with a Rett-like phenotype. Subsequently CDKL5 mutations were shown to be associated with more diverse phenotypes including mild epilepsy and autism without epilepsy. Furthermore, CDKL5 mutations were found in patients with Angelman-like phenotype. The severity of epilepsy associated with CDKL5 mutations was recently shown to correlate with the type of CDKL5 mutations and epilepsy was identified to involve three distinct sequential stages. Here, we describe the phenotype of a severe form of neurodevelopmental disease in a female patient with a de novo nonsense mutation of the CDKL5 gene c.175C > T (p.R59X) affecting the catalytic domain of CDKL5 protein. Mutations in the CDKL5 gene are less common in males and can be associated with a genomic deletion as found in our male patient with a deletion of 0.3 Mb at Xp22.13 including the CDKL5 gene. We review phenotypes associated with CDKL5 mutations and examine putative relationships between the clinical epilepsy phenotype and the type of the mutation in the CDKL5 gene.
authors.affiliation: Rinnekoti Foundation, Rinnekodintie 10, FIN-02980 Espoo, Finland. maija.castren@rinnekoti.fi
authors.forename: Maija
authors.initials: M
authors.lastname: Castrén
authors.forename: Eija
authors.initials: E
authors.lastname: Gaily
authors.forename: Carola
authors.initials: C
authors.lastname: Tengström
authors.forename: Jaana
authors.initials: J
authors.lastname: Lähdetie
authors.forename: Hayley
authors.initials: H
authors.lastname: Archer
authors.forename: Sirpa
authors.initials: S
authors.lastname: Ala-Mello
mesh_terms: D001145:Arrhythmias, Cardiac / Q000201:enzymology / Q000235:genetics; D002648:Child; D018389:Codon, Nonsense / Q000235:genetics*; D002658:Developmental Disabilities / Q000201:enzymology / Q000235:genetics; D004827:Epilepsy / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000201:enzymology / Q000235:genetics; D008297:Male; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human