title: PLCB1 epileptic encephalopathies; Review and expansion of the phenotypic spectrum.
abstract: BACKGROUND
  Biallelic loss-of-function mutations of phospholipase C-β1 (PLCB1) have been described in three children with an early onset epileptic encephalopathy (EE). In two of them a homozygous deletion of the promotor and first three coding exons was found. The third patient had an almost identical heterozygous deletion in combination with a heterozygous splice site variant. All patients had intractable epilepsy and a severe developmental delay.
  
  
  RESULTS
  We present the case of a boy with an infantile EE starting at the age of four months with a fever induced status epilepticus, modified hypsarrhythmia and developmental regression. The epilepsy was reasonably controlled with corticoids and valproate whereupon generalized tonic-clonic seizures appeared only each 3-4 months. However, only a slow developmental progress was seen hereafter, resulting in a severe intellectual disability with absent speech, motor delay and autistic features. We identified a novel homozygous partial deletion of PLCB1, affecting exons 7-9.
  
  
  CONCLUSIONS
  This report emphasizes the role of PLCB1 haploinsufficiency in severe EE. We demonstrate a phenotypic variability in patients with a PLCB1-associated EE. In addition, our findings underscore the importance of microarray analysis in all patients with an EE of unknown etiology.
authors.affiliation: Department of Neurology-Pediatric Neurology, University and University Hospital Antwerp, Antwerp, Belgium. Electronic address: an-sofie.schoonjans@uza.be.
authors.forename: An-Sofie
authors.initials: AS
authors.lastname: Schoonjans
authors.affiliation: Department of Medical Genetics, University and University Hospital Antwerp, Antwerp, Belgium.
authors.forename: Marije
authors.initials: M
authors.lastname: Meuwissen
authors.affiliation: Department of Medical Genetics, University and University Hospital Antwerp, Antwerp, Belgium.
authors.forename: Edwin
authors.initials: E
authors.lastname: Reyniers
authors.affiliation: Department of Medical Genetics, University and University Hospital Antwerp, Antwerp, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Kooy
authors.affiliation: Department of Neurology-Pediatric Neurology, University and University Hospital Antwerp, Antwerp, Belgium.
authors.forename: Berten
authors.initials: B
authors.lastname: Ceulemans
mesh_terms: D002658:Developmental Disabilities / Q000235:genetics; D004827:Epilepsy / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D009154:Mutation / Q000235:genetics*; D054799:Phospholipase C beta / Q000235:genetics*; D013036:Spasms, Infantile / Q000235:genetics
chemical_list: D054799:Phospholipase C beta
keywords: Copy number variant (CNV); Early onset epileptic encephalopathy; Phospholipase C beta 1 (PLCB1)