title: A subset of genomic alterations detected in rolandic epilepsies contains candidate or known epilepsy genes including GRIN2A and PRRT2.
abstract: OBJECTIVE
  Rolandic epilepsies (REs) represent the most frequent epilepsy in childhood. Patients may experience cognitive, speech, language, reading, and behavioral issues. The genetic origin of REs has long been debated. The participation of rare copy number variations (CNVs) in the pathophysiology of various human epilepsies has been increasingly recognized. However, no systematic search for microdeletions or microduplications has been reported in RE so far.
  
  
  METHODS
  Array comparative genomic hybridization (aCGH) and quantitative polymerase chain reaction (qPCR) were used to analyze the genomic status of a series of 47 unrelated RE patients who displayed various types of electroclinical manifestations.
  
  
  RESULTS
  Thirty rare CNVs were detected in 21 RE patients. Two CNVs were de novo, 12 were inherited, and 16 were of unknown inheritance. Each CNV was unique to one given patient, except for a 16p11.2 duplication found in two patients. The CNVs of highest interest comprised or disrupted strong candidate or confirmed genes for epileptic and other neurodevelopmental disorders, including BRWD3, GRIN2A, KCNC3, PRKCE, PRRT2, SHANK1, and TSPAN7.
  
  
  CONCLUSIONS
  Patients with REs showed rare microdeletions and microduplications with high frequency and heterogeneity. Whereas only a subset of all genomic alterations found here may actually participate in the phenotype, the novel de novo events as well as several inherited CNVs contain or disrupt genes, some of which are likely to influence the emergence, the presentation, or the comorbidity of RE. The future screening of cohorts of larger size will help in detecting more de novo or recurrent events and in appreciating the possible enrichment of specific CNVs in patients with RE.
authors.affiliation: Department of Genetics, Lyon University Hospital, Lyon, France; Claude Bernard Lyon I University, Lyon, France; CRNL, CNRS UMR 5292, INSERM U1028, Lyon, France.
authors.forename: Sarra
authors.initials: S
authors.lastname: Dimassi
authors.forename: Audrey
authors.initials: A
authors.lastname: Labalme
authors.forename: Gaetan
authors.initials: G
authors.lastname: Lesca
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Rudolf
authors.forename: Nadine
authors.initials: N
authors.lastname: Bruneau
authors.forename: Edouard
authors.initials: E
authors.lastname: Hirsch
authors.forename: Alexis
authors.initials: A
authors.lastname: Arzimanoglou
authors.forename: Jacques
authors.initials: J
authors.lastname: Motte
authors.forename: Anne
authors.initials: A
authors.lastname: de Saint Martin
authors.forename: Nadia
authors.initials: N
authors.lastname: Boutry-Kryza
authors.forename: Robin
authors.initials: R
authors.lastname: Cloarec
authors.forename: Afaf
authors.initials: A
authors.lastname: Benitto
authors.forename: Agnès
authors.initials: A
authors.lastname: Ameil
authors.forename: Patrick
authors.initials: P
authors.lastname: Edery
authors.forename: Philippe
authors.initials: P
authors.lastname: Ryvlin
authors.forename: Julitta
authors.initials: J
authors.lastname: De Bellescize
authors.forename: Pierre
authors.initials: P
authors.lastname: Szepetowski
authors.forename: Damien
authors.initials: D
authors.lastname: Sanlaville
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D056915:DNA Copy Number Variations / Q000235:genetics; D019305:Epilepsy, Rolandic / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D018740:Genetic Heterogeneity; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C569370:PRRT2 protein, human
keywords: 16p11.2 duplication; Array-CGH; GRIN2A; PRRT2; Rolandic epilepsy