title: CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy.
abstract: OBJECTIVE
  To search for CDKL5 gene mutations in boys presenting with severe early-onset encephalopathy and intractable epilepsy, a clinical picture very similar to that already described in girls with CDKL5 mutations.
  
  
  METHODS
  Eight boys (age range 3-16 years, mean age 8.5 years, SD 4.38) with severe or profound mental retardation and early-onset intractable seizures were selected for CDKL5 gene mutation screening by denaturing high-performance liquid chromatography analysis.
  
  
  RESULTS
  We found three unrelated boys carrying three different missense mutations of the CDKL5 gene: c.872G>A (p.C291Y), c.863C>T (p.T288I), and c.533G>C (p.R178P). They presented early-onset, polymorphous, and drug-resistant seizures, mostly myoclonic and tonic or spasms. EEG showed epileptiform abnormalities which were multifocal during wakefulness, and pseudoperiodic bisynchronous during sleep.
  
  
  CONCLUSIONS
  This study describes three boys carrying CDKL5 missense mutations and their detailed clinical and EEG data, and indicates that CDKL5 gene mutations may represent a cause of severe or profound mental retardation and early-onset intractable seizures, also in boys. Screening for CDKL5 mutations is strongly recommended in individuals with these clinical features.
authors.affiliation: Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS), Via Conte Ruggero 73, 94018 Troina (EN), Italy. melia@oasi.en.it
authors.forename: M
authors.initials: M
authors.lastname: Elia
authors.forename: M
authors.initials: M
authors.lastname: Falco
authors.forename: R
authors.initials: R
authors.lastname: Ferri
authors.forename: A
authors.initials: A
authors.lastname: Spalletta
authors.forename: M
authors.initials: M
authors.lastname: Bottitta
authors.forename: G
authors.initials: G
authors.lastname: Calabrese
authors.forename: M
authors.initials: M
authors.lastname: Carotenuto
authors.forename: S A
authors.initials: SA
authors.lastname: Musumeci
authors.forename: M
authors.initials: M
authors.lastname: Lo Giudice
authors.forename: M
authors.initials: M
authors.lastname: Fichera
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D001927:Brain Diseases / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human