title: CDKL5 and ARX mutations in males with early-onset epilepsy.
abstract: Mutations in CDKL5 and ARX are known causes of early-onset epilepsy and severe developmental delay in males and females. Although numerous males with ARX mutations associated with various phenotypes have been reported in the literature, the majority of CDKL5 mutations have been identified in females with a phenotype characterized by early-onset epilepsy, severe global developmental delay, absent speech, and stereotypic hand movements. To date, only 10 males with CDKL5 mutations have been reported. Our retrospective study reports on the clinical, neuroimaging, and molecular findings of 18 males with early-onset epilepsy caused by either CDKL5 or ARX mutations. These 18 patients include eight new males with CDKL5 mutations and 10 with ARX mutations identified through sequence analysis of 266 and 346 males, respectively, at our molecular diagnostic laboratory. Our large dataset therefore expands on the number of reported males with CDKL5 mutations and highlights that aberrations of CDKL5 and ARX combined are an important consideration in the genetic forms of early-onset epilepsy in boys.
authors.affiliation: Division of Genetic Medicine, Department of Pediatrics, University of Washington and Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington 98101, USA. gmirzaa@uw.edu
authors.forename: Ghayda M
authors.initials: GM
authors.lastname: Mirzaa
authors.forename: Alex R
authors.initials: AR
authors.lastname: Paciorkowski
authors.forename: Eric D
authors.initials: ED
authors.lastname: Marsh
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Berry-Kravis
authors.forename: Livija
authors.initials: L
authors.lastname: Medne
authors.forename: Asem
authors.initials: A
authors.lastname: Alkhateeb
authors.forename: Art
authors.initials: A
authors.lastname: Grix
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Wirrell
authors.forename: Berkley R
authors.initials: BR
authors.lastname: Powell
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Nickels
authors.forename: Barbara
authors.initials: B
authors.lastname: Burton
authors.forename: Andrea
authors.initials: A
authors.lastname: Paras
authors.forename: Katherine
authors.initials: K
authors.lastname: Kim
authors.forename: Wendy
authors.initials: W
authors.lastname: Chung
authors.forename: William B
authors.initials: WB
authors.lastname: Dobyns
authors.forename: Soma
authors.initials: S
authors.lastname: Das
mesh_terms: D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D004569:Electroencephalography; D004827:Epilepsy / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D009154:Mutation / Q000235:genetics* / Q000502:physiology; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D012640:Seizures / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C469264:ARX protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors; D004247:DNA; D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human