title: Protocadherin 19 mutations in girls with infantile-onset epilepsy.
abstract: OBJECTIVE
  To explore the causative role of PCDH19 gene (Xq22) in female patients with epilepsy.
  
  
  METHODS
  We studied a cohort of 117 female patients with febrile seizures (FS) and a wide spectrum of epilepsy phenotypes including focal and generalized forms with either sporadic or familial distribution.
  
  
  RESULTS
  PCDH19 screening showed point mutations in 13 probands (11%). Mean age at seizure onset was 8.5 months; 8 patients (62%) presented with FS, 4 (33%) with cluster of focal seizures, and 1 with de novo status epilepticus (SE). Subsequent seizure types included afebrile tonic-clonic, febrile, and afebrile SE, absences, myoclonic, and focal seizures. Seven patients (54%) had a clinical diagnosis consistent with Dravet syndrome (DS); 6 (46%) had focal epilepsy. In most patients, seizures were particularly frequent at onset, manifesting in clusters and becoming less frequent with age. Mental retardation was present in 11 patients, ranging from mild (7; 64%) to moderate (1; 9%) to severe (3; 27%). Five patients (38%) had autistic features in association to mental retardation. Mutations were missense (6), truncating (2), frameshift (3), and splicing (2). Eleven were new mutations. Mutations were inherited in 3 probands (25%): 2 from apparently unaffected fathers and 1 from a mother who had had generalized epilepsy.
  
  
  CONCLUSIONS
  PCDH19 is emerging as a major gene for infantile-onset familial or sporadic epilepsy in female patients with or without mental retardation. In our cohort, epileptic encephalopathy with DS-like features and focal epilepsy of variable severity were the associated phenotypes and were equally represented.
authors: Child Neurology Unit, Children's Hospital A. Meyer, Viale Pieraccini 24, 50139 Firenze, Italy.
authors: C
authors: C
authors: Marini
authors: D
authors: D
authors: Mei
authors: L
authors: L
authors: Parmeggiani
authors: V
authors: V
authors: Norci
authors: E
authors: E
authors: Calado
authors: A
authors: A
authors: Ferrari
authors: A
authors: A
authors: Moreira
authors: T
authors: T
authors: Pisano
authors: N
authors: N
authors: Specchio
authors: F
authors: F
authors: Vigevano
authors: D
authors: D
authors: Battaglia
authors: R
authors: R
authors: Guerrini
mesh_terms: D017668:Age of Onset; D015820:Cadherins / Q000235:genetics*; D004569:Electroencephalography / Q000379:methods; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging / Q000379:methods; D017354:Point Mutation / Q000235:genetics*; D000091363:Protocadherins; D003294:Seizures, Febrile / Q000235:genetics* / Q000503:physiopathology
chemical_list: D015820:Cadherins; C438605:PCDH19 protein, human; D000091363:Protocadherins