title: Somatic mosaicism of a CDKL5 mutation identified by next-generation sequencing.
abstract: BACKGROUND
  CDKL5-related encephalopathy is an X-linked dominantly inherited disorder that is characterized by early infantile epileptic encephalopathy or atypical Rett syndrome. We describe a 5-year-old Japanese boy with intractable epilepsy, severe developmental delay, and Rett syndrome-like features. Onset was at 2 months, when his electroencephalogram showed sporadic single poly spikes and diffuse irregular poly spikes.
  
  
  METHODS
  We conducted a genetic analysis using an Illumina® TruSight™ One sequencing panel on a next-generation sequencer.
  
  
  RESULTS
  We identified two epilepsy-associated single nucleotide variants in our case: CDKL5 p.Ala40Val and KCNQ2 p.Glu515Asp. CDKL5 p.Ala40Val has been previously reported to be responsible for early infantile epileptic encephalopathy. In our case, the CDKL5 heterozygous mutation showed somatic mosaicism because the boy's karyotype was 46,XY. The KCNQ2 variant p.Glu515Asp is known to cause benign familial neonatal seizures-1, and this variant showed paternal inheritance.
  
  
  CONCLUSIONS
  Although we believe that the somatic mosaic CDKL5 mutation is mainly responsible for the neurological phenotype in the patient, the KCNQ2 variant might have some neurological effect. Genetic analysis by next-generation sequencing is capable of identifying multiple variants in a patient.
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address: morisada@med.kobe-u.ac.jp.
authors.forename: Naoya
authors.initials: N
authors.lastname: Morisada
authors.affiliation: Department of Neurology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagase
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishiyama
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Daisaku
authors.initials: D
authors.lastname: Toyoshima
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Neurology, Hyogo Prefectural Kobe Children's Hospital, Kobe, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Maruyama
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Xue Jun
authors.initials: XJ
authors.lastname: Fu
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Kandai
authors.initials: K
authors.lastname: Nozu
authors.affiliation: Medical Welfare Center Sakura, Sanda, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Wada
authors.affiliation: Kobe University Graduate School of Health Science, Kobe, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takada
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Iijima
mesh_terms: D058540:Aicardi Syndrome / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002675:Child, Preschool; D006801:Humans; D008297:Male; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013036:Spasms, Infantile / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology
chemical_list: D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human
keywords: CDKL5; Double mutations; Early infantile epileptic encephalopathy (EIEE); Next-generation sequencing; Somatic mosaicism