TY - JOUR
T1 - Clinical significance of rare copy number variations in epilepsy
T2 - A case-control survey using microarray-based comparative genomic hybridization
AU - Striano, Pasquale
AU - Coppola, Antonietta
AU - Paravidino, Roberta
AU - Malacarne, Michela
AU - Gimelli, Stefania
AU - Robbiano, Angela
AU - Traverso, Monica
AU - Pezzella, Marianna
AU - Belcastro, Vincenzo
AU - Bianchi, Amedeo
AU - Elia, Maurizio
AU - Falace, Antonio
AU - Gazzerro, Elisabetta
AU - Ferlazzo, Edoardo
AU - Freri, Elena
AU - Galasso, Roberta
AU - Gobbi, Giuseppe
AU - Molinatto, Cristina
AU - Cavani, Simona
AU - Zuffardi, Orsetta
AU - Striano, Salvatore
AU - Ferrero, Giovanni Battista
AU - Silengo, Margherita
AU - Cavaliere, Maria Luigia
AU - Benelli, Matteo
AU - Magi, Alberto
AU - Piccione, Maria
AU - Bricarelli, Franca Dagna
AU - Coviello, Domenico A.
AU - Fichera, Marco
AU - Minetti, Carlo
AU - Zara, Federico
PY - 2012/3
Y1 - 2012/3
N2 - Objective: To perform an extensive search for genomic rearrangements by microarray-based comparative genomic hybridization in patients with epilepsy. Design: Prospective cohort study. Setting: Epilepsy centers in Italy. Patients: Two hundred seventy-nine patients with unexplained epilepsy, 265 individuals with nonsyndromic mental retardation but no epilepsy, and 246 healthy control subjects were screened by microarray-based comparative genomic hybridization. Main Outcomes Measures: Identification of copy number variations (CNVs) and gene enrichment. Results: Rare CNVs occurred in 26 patients (9.3%) and 16 healthy control subjects (6.5%) (P=.26). The CNVs identified in patients were larger (P=.03) and showed higher gene content (P=.02) than those in control subjects. The CNVslarger than 1 megabase (P=.002) and including more than 10 genes (P=.005) occurred more frequently in patients than in control subjects. Nine patients (34.6%) among those harboring rare CNVs showed rearrangements associatedwith emerging microdeletion or microduplication syndromes. Mental retardation and neuropsychiatric features were associated with rare CNVs (P=.004), whereas epilepsy type was not. The CNV rate in patients with epilepsy and mental retardation or neuropsychiatric features is not different from that observed in patients with mental retardation only. Moreover, significant enrichment of genes involved in ion transport was observed within CNVs identified in patients with epilepsy. Conclusions: Patients with epilepsy show a significantly increased burden of large, rare, gene-rich CNVs, particularly when associated with mental retardation and neuropsychiatric features. The limited overlap betweenCNVsobserved in the epilepsy group and those observed in the group with mental retardation only as well as the involvement of specific (ion channel) genes indicate a specific association between the identified CNVs and epilepsy. Screening for CNVs should be performed for diagnostic purposes preferentially in patients with epilepsy and mental retardation or neuropsychiatric features.
AB - Objective: To perform an extensive search for genomic rearrangements by microarray-based comparative genomic hybridization in patients with epilepsy. Design: Prospective cohort study. Setting: Epilepsy centers in Italy. Patients: Two hundred seventy-nine patients with unexplained epilepsy, 265 individuals with nonsyndromic mental retardation but no epilepsy, and 246 healthy control subjects were screened by microarray-based comparative genomic hybridization. Main Outcomes Measures: Identification of copy number variations (CNVs) and gene enrichment. Results: Rare CNVs occurred in 26 patients (9.3%) and 16 healthy control subjects (6.5%) (P=.26). The CNVs identified in patients were larger (P=.03) and showed higher gene content (P=.02) than those in control subjects. The CNVslarger than 1 megabase (P=.002) and including more than 10 genes (P=.005) occurred more frequently in patients than in control subjects. Nine patients (34.6%) among those harboring rare CNVs showed rearrangements associatedwith emerging microdeletion or microduplication syndromes. Mental retardation and neuropsychiatric features were associated with rare CNVs (P=.004), whereas epilepsy type was not. The CNV rate in patients with epilepsy and mental retardation or neuropsychiatric features is not different from that observed in patients with mental retardation only. Moreover, significant enrichment of genes involved in ion transport was observed within CNVs identified in patients with epilepsy. Conclusions: Patients with epilepsy show a significantly increased burden of large, rare, gene-rich CNVs, particularly when associated with mental retardation and neuropsychiatric features. The limited overlap betweenCNVsobserved in the epilepsy group and those observed in the group with mental retardation only as well as the involvement of specific (ion channel) genes indicate a specific association between the identified CNVs and epilepsy. Screening for CNVs should be performed for diagnostic purposes preferentially in patients with epilepsy and mental retardation or neuropsychiatric features.
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U2 - 10.1001/archneurol.2011.1999
DO - 10.1001/archneurol.2011.1999
M3 - Article
C2 - 22083797
AN - SCOPUS:84858602053
VL - 69
SP - 322
EP - 330
JO - Archives of Neurology
JF - Archives of Neurology
SN - 0003-9942
IS - 3
ER -