title: CDKL5 alterations lead to early epileptic encephalopathy in both genders.
abstract: OBJECTIVE
  Genetic mutations of the cyclin-dependent kinase-like 5 gene (CDKL5) have been reported in patients with epileptic encephalopathy, which is characterized by intractable seizures and severe-to-profound developmental delay. We investigated the clinical relevance of CDKL5 alterations in both genders.
  
  
  METHODS
  A total of 125 patients with epileptic encephalopathy were examined for genomic copy number aberrations, and 119 patients with no such aberrations were further examined for CDKL5 mutations. Five patients with Rett syndrome, who did not show methyl CpG-binding protein 2 gene (MECP2) mutations, were also examined for CDKL5 mutations.
  
  
  RESULTS
  One male and three female patients showed submicroscopic deletions including CDKL5, and two male and six female patients showed CDKL5 nucleotide alterations. Development of early onset seizure was a characteristic clinical feature for the patients with CDKL5 alterations in both genders despite polymorphous seizure types, including myoclonic seizures, tonic seizures, and spasms. Severe developmental delays and mild frontal lobe atrophies revealed by brain magnetic resonance imaging (MRI) were observed in almost all patients, and there was no gender difference in phenotypic features.
  
  
  CONCLUSIONS
  We observed that 5% of the male patients and 14% of the female patients with epileptic encephalopathy had CDKL5 alterations. These findings indicate that alterations in CDKL5 are associated with early epileptic encephalopathy in both female and male patients.
authors.affiliation: Tokyo Women's Medical University Institute for Integrated Medical Sciences, Shinjuku-ward, Tokyo, Japan.
authors.forename: Jao-Shwann
authors.initials: JS
authors.lastname: Liang
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimojima
authors.forename: Rumiko
authors.initials: R
authors.lastname: Takayama
authors.forename: Jun
authors.initials: J
authors.lastname: Natsume
authors.forename: Minobu
authors.initials: M
authors.lastname: Shichiji
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hirasawa
authors.forename: Kaoru
authors.initials: K
authors.lastname: Imai
authors.forename: Tohru
authors.initials: T
authors.lastname: Okanishi
authors.forename: Seiji
authors.initials: S
authors.lastname: Mizuno
authors.forename: Akihisa
authors.initials: A
authors.lastname: Okumura
authors.forename: Midori
authors.initials: M
authors.lastname: Sugawara
authors.forename: Tomoshiro
authors.initials: T
authors.lastname: Ito
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ikeda
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Oguni
authors.forename: Katsumi
authors.initials: K
authors.lastname: Imai
authors.forename: Makiko
authors.initials: M
authors.lastname: Osawa
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics; D004569:Electroencephalography; D004827:Epilepsy / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012737:Sex Factors
chemical_list: D018389:Codon, Nonsense; D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human