title: Copy number variations and susceptibility to lateral temporal epilepsy: a study of 21 pedigrees.
abstract: OBJECTIVE
  Autosomal dominant lateral temporal epilepsy (ADLTE) is a focal epileptic syndrome characterized by auditory or aphasic auras. Mutations in the LGI1 gene account for <50% of ADLTE families. To identify copy number variants (CNVs) related to ADLTE, we examined a collection of ADLTE families without LGI1 mutations.
  
  
  METHODS
  Twenty-one families were included based on a history of focal seizures with auditory and/or receptive aphasic symptoms in two or more individuals, absence of brain abnormalities, and negative LGI1 test. DNA suitable for single nucleotide polymorphism-array analysis was genotyped using the high-density HumanOmni1-Quad v1.0 beadchip (Illumina). CNVs were inferred using the PennCNV algorithm. Selected CNVs were validated by real-time quantitative polymerase chain reaction (qPCR).
  
  
  RESULTS
  We analyzed 62 affected and 114 unaffected members of our study families and identified a total of 11,214 CNVs, corresponding to 1,890 unique regions with an average size of 67.3 kb. Most CNVs were <50 kb, whereas a small proportion (1.2%) exceeded 500 kb. We identified 12 rare CNVs that segregated with lateral temporal epilepsy in single families. Particularly, we found rare microdeletions within or near two genes, RBFOX1 and NRXN1, previously shown to harbor deletions associated with idiopathic generalized epilepsy, and a microduplication in the proximal region of chromosome 1q21.1, where duplications have been associated with various neurodevelopmental disorders and epilepsy. We also found numerous polymorphic CNVs in the affected members of one or more families, including a deletion of the PCDHA8/10 genes, which was enriched in the patients of our family cohort.
  
  
  CONCLUSIONS
  Our results provide clues on genes for susceptibility to ADLTE, particularly in those families where the inheritance pattern is less compatible with autosomal dominance. Some of these genes also confer risk for other epilepsy syndromes.
authors.affiliation: Porto Conte Ricerche, Alghero, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Fanciulli
authors.forename: Elena
authors.initials: E
authors.lastname: Pasini
authors.forename: Sandro
authors.initials: S
authors.lastname: Malacrida
authors.forename: Pasquale
authors.initials: P
authors.lastname: Striano
authors.forename: Salvatore
authors.initials: S
authors.lastname: Striano
authors.forename: Roberto
authors.initials: R
authors.lastname: Michelucci
authors.forename: Ruth
authors.initials: R
authors.lastname: Ottman
authors.forename: Carlo
authors.initials: C
authors.lastname: Nobile
mesh_terms: D056915:DNA Copy Number Variations / Q000235:genetics*; D004833:Epilepsy, Temporal Lobe / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D060005:Genotyping Techniques; D006801:Humans; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
keywords: Copy number variation; Genomics; Susceptibility genes; Temporal lobe epilepsy