title: CDKL5 gene status in female patients with epilepsy and Rett-like features: two new mutations in the catalytic domain.
abstract: BACKGROUND
  Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) located in the Xp22 region have been shown to cause a subset of atypical Rett syndrome with infantile spasms or early seizures starting in the first postnatal months.
  
  
  METHODS
  We performed mutation screening of CDKL5 in 60 female patients who had been identified as negative for the methyl CpG-binding protein 2 gene (MECP2) mutations, but who had current or past epilepsy, regardless of the age of onset, type, and severity. All the exons in the CDKL5 gene and their neighbouring sequences were examined, and CDKL5 rearrangements were studied by multiplex ligation-dependent probe amplification (MLPA).
  
  
  RESULTS
  Six previously unidentified DNA changes were detected, two of which were disease-causing mutations in the catalytic domain: a frameshift mutation (c.509_510insGT; p.Glu170GlyfsX36) and a complete deletion of exon 10. Both were found in patients with seizures that started in the first month of life.
  
  
  CONCLUSIONS
  This study demonstrated the importance of CDKL5 mutations as etiological factors in neurodevelopmental disorders, and indicated that a thorough analysis of the CDKL5 gene sequence and its rearrangements should be considered in females with Rett syndrome-like phenotypes, severe encephalopathy and epilepsy with onset before 5 months of age. This study also confirmed the usefulness of MLPA as a diagnostic screening method for use in clinical practice.
authors.affiliation: Laboratorio de Genética Molecular, Servicio de Genética, Hospital Universitario Cruces, Instituto BioCruces, Barakaldo-Bizkaia, Spain.
authors.forename: Hiart
authors.initials: H
authors.lastname: Maortua
authors.forename: Cristina
authors.initials: C
authors.lastname: Martínez-Bouzas
authors.forename: María-Teresa
authors.initials: MT
authors.lastname: Calvo
authors.forename: Maria-Rosario
authors.initials: MR
authors.lastname: Domingo
authors.forename: Feliciano
authors.initials: F
authors.lastname: Ramos
authors.forename: Ainhoa
authors.initials: A
authors.lastname: García-Ribes
authors.forename: María-Jesús
authors.initials: MJ
authors.lastname: Martínez
authors.forename: María-Asunción
authors.initials: MA
authors.lastname: López-Aríztegui
authors.forename: Nerea
authors.initials: N
authors.lastname: Puente
authors.forename: Izaskun
authors.initials: I
authors.lastname: Rubio
authors.forename: María-Isabel
authors.initials: MI
authors.lastname: Tejada
mesh_terms: D017668:Age of Onset; D001483:Base Sequence; D020134:Catalytic Domain / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000235:genetics; D004827:Epilepsy / Q000235:genetics*; D005091:Exons; D005260:Female; D015321:Gene Rearrangement; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D008969:Molecular Sequence Data; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015518:Rett Syndrome / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human