title: Mutation screening of the CDKL5 gene in cryptogenic infantile intractable epilepsy and review of clinical sensitivity.
abstract: OBJECTIVE
  To perform CDKL5 mutation screening in Thai children with cryptogenic infantile intractable epilepsy and to determine the clinical sensitivity of CDKL5 screening when different inclusion criteria were applied.
  
  
  METHODS
  Children with cryptogenic infantile intractable epilepsy were screened for CDKL5 mutation using multiplex ligation-dependent probe amplification and DNA sequencing. The clinical sensitivity was reviewed by combining the results of studies using similar inclusion screening criteria.
  
  
  RESULTS
  Thirty children (19 girls and 11 boys) with a median seizure onset of 7 months were screened. Almost a half had infantile spasms and one fifth had stereotypic hand movements. A novel c.2854C>T (p.R952X) was identified in an ambulatory girl who had severe mental retardation, multiple types of seizures without Rett-like features. Her mother had a mild intellectual disability, yet her grandmother and half sister were normal despite having the same genetic alteration (random X-inactivation patterns). The pathogenicity of p.R952X identified here was uncertain since healthy relatives and 6 female controls also harbor this alteration. The clinical sensitivity of CDKL5 mutation screening among females with Rett-like features and negative MECP2 screening was 7.8% while the clinical sensitivity among females having cryptogenic intractable seizures with an onset before the ages of 12, 6 and 3 months were 4.7, 11.6 and 14.3%, respectively.
authors.affiliation: Department of Pediatrics, Prince of Songkla University, Thailand.
authors.forename: Utcharee
authors.initials: U
authors.lastname: Intusoma
authors.forename: Fadell
authors.initials: F
authors.lastname: Hayeeduereh
authors.forename: Oradawan
authors.initials: O
authors.lastname: Plong-On
authors.forename: Thanya
authors.initials: T
authors.lastname: Sripo
authors.forename: Punnee
authors.initials: P
authors.lastname: Vasiknanonte
authors.forename: Supachai
authors.initials: S
authors.lastname: Janjindamai
authors.forename: Apasri
authors.initials: A
authors.lastname: Lusawat
authors.forename: Sasipa
authors.initials: S
authors.lastname: Thammongkol
authors.forename: Anannit
authors.initials: A
authors.lastname: Visudtibhan
authors.forename: Pornprot
authors.initials: P
authors.lastname: Limprasert
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011446:Prospective Studies; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013036:Spasms, Infantile / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D013785:Thailand; D049951:X Chromosome Inactivation / Q000235:genetics
chemical_list: D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human