title: A novel CDKL5 mutation in a 47,XXY boy with the early-onset seizure variant of Rett syndrome.
abstract: Mutations of the cyclin-dependent kinase-like 5 gene (CDKL5), reported almost exclusively in female subjects, have been recently found to be the cause of a phenotype overlapping Rett syndrome with early-onset epileptic encephalopathy. We describe the first CDKL5 mutation detected in a male individual with 47,XXY karyotype. This previously unreported, de novo, mutation truncates the large CDKL5 COOH-terminal region, thought to be crucial for the proper sub-cellular localization of the CDKL5 protein. The resulting phenotype is characterized by a severe early-onset epileptic encephalopathy, global developmental delay, and profound intellectual and motor impairment with features reminiscent of Rett syndrome. In light of the data presented we discuss the possible phenotypic modulatory effects of the supernumerary wild type X allele and pattern of X chromosome inactivation and stress the importance of considering the causal involvement of CDKL5 in developmentally delayed males with early-onset seizures.
authors.affiliation: Department of Pediatrics, Pediatric Neurology Unit, University of Padua, Padua, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Sartori
authors.forename: Gabriella
authors.initials: G
authors.lastname: Di Rosa
authors.forename: Roberta
authors.initials: R
authors.lastname: Polli
authors.forename: Elisa
authors.initials: E
authors.lastname: Bettella
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tricomi
authors.forename: Gaetano
authors.initials: G
authors.lastname: Tortorella
authors.forename: Alessandra
authors.initials: A
authors.lastname: Murgia
mesh_terms: D017668:Age of Onset; D002658:Developmental Disabilities; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015518:Rett Syndrome / Q000235:genetics*; D012640:Seizures / Q000235:genetics; D025064:Sex Chromosome Disorders; D049951:X Chromosome Inactivation
chemical_list: D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human