Clinical Significance of Rare Copy NumberVariations in Epilepsy. A Case-Control Survey Using Microarray-Based ComparativeGenomic Hybridization

Maria Piccione, Antonietta Coppola, Roberta Paravidino, Antonio Falace, Vincenzo Belcastro, Marianna Pezzella, Stefania Gimelli, Cristina Molinatto, Roberta Galasso, Angela Robbiano, Roberta Galasso, Edoardo Ferlazzo, Roberta Galasso, Elena Freri, Simona Cavani, Michela Malacarne, Elisabetta Gazzerro, Franca Dagna Bricarelli, Monica Traverso, Pasquale StrianoFederico Zara, Domenico A. Coviello, Maria Piccione, Marco Fichera, Maria Luigia Cavaliere, Orsetta Zuffardi, Carlo Minetti, Margherita Silengo, Giuseppe Gobbi, Giovanni Battista Ferrero, Salvatore Striano, Maurizio Elia, Amedeo Bianchi

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59 Citations (Scopus)


Objective: To perform an extensive search for genomicrearrangements by microarray-based comparativegenomic hybridization in patients with epilepsy.Design: Prospective cohort study.Setting: Epilepsy centers in Italy.Patients: Two hundred seventy-nine patients with unexplainedepilepsy, 265 individuals with nonsyndromicmental retardation but no epilepsy, and 246 healthy controlsubjects were screened by microarray-based comparativegenomic hybridization.Main Outcomes Measures: Identification of copy numbervariations (CNVs) and gene enrichment.Results: Rare CNVs occurred in 26 patients (9.3%) and16 healthy control subjects (6.5%) (P=.26). TheCNVsidentifiedin patients were larger (P=.03) and showed highergene content (P=.02) than those in control subjects. TheCNVslarger than 1 megabase (P=.002) and including morethan 10 genes (P=.005) occurred more frequently in patientsthan in control subjects. Nine patients (34.6%) amongthose harboring rare CNVs showed rearrangements associatedwith emerging microdeletion or microduplicationsyndromes. Mental retardation and neuropsychiatric featureswere associated with rare CNVs (P=.004), whereasepilepsy type was not. The CNV rate in patients with epilepsyand mental retardation or neuropsychiatric featuresis not different from that observed in patients with mentalretardation only. Moreover, significant enrichment of genesinvolved in ion transport was observed within CNVs identifiedin patients with epilepsy.Conclusions: Patients with epilepsy show a significantlyincreased burden of large, rare, gene-rich CNVs, particularlywhen associated with mental retardation and neuropsychiatricfeatures. The limited overlap betweenCNVsobservedin the epilepsy group and those observed in the groupwith mental retardation only as well as the involvement ofspecific (ion channel) genes indicate a specific associationbetween the identified CNVs and epilepsy. Screening forCNVs should be performed for diagnostic purposes preferentiallyin patients with epilepsy and mental retardation or neuropsychiatric features.
Original languageEnglish
Pages (from-to)322-330
Number of pages9
JournalArchives of Neurology
Publication statusPublished - 2012

All Science Journal Classification (ASJC) codes

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology


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