title: Detection of microchromosomal aberrations in refractory epilepsy: a pilot study.
abstract: Seizures often occur in patients with microchromosomal aberrations responsible for moderate to severe intellectual disability. We hypothesised that epilepsy alone could be caused by microdeletions or microduplications, which might also relate to epilepsy refractory to medication. Chromosomes from 20 subjects with epilepsy and repeated failure of antiepileptic medication were examined using molecular methods. Firstly, the 41 subtelomeric regions were scanned using fluorescence in situ hybridization and multiplex ligation-dependent probe amplification. Secondly, a genome-wide scan was carried out using oligonucleotide-array comparative genome hybridisation on two platforms: Nimblegen and Agilent. Two aberrations (2/20) were identified: a recurrent microdeletion at 15q13.3 previously characterised in patients with seizures that generally respond to medication, and a novel 1.15 Mb microchromosomal duplication at 10q21.2 also present in the unaffected mother. We conclude that gene content of microchromosomal aberrations is not a major cause of refractory seizures, but that microchromosomal anomalies are found in an appreciable fraction of such cases.
authors.affiliation: Department of Medicine, University of Melbourne, Australia.
authors.forename: Jacinta M
authors.initials: JM
authors.lastname: McMahon
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: Jillian K
authors.initials: JK
authors.lastname: Nicholl
authors.forename: Wendy
authors.initials: W
authors.lastname: Waters
authors.forename: Helen
authors.initials: H
authors.lastname: Eyre
authors.forename: Lyn
authors.initials: L
authors.lastname: Hinton
authors.forename: Paul
authors.initials: P
authors.lastname: Nelson
authors.forename: Sui
authors.initials: S
authors.lastname: Yu
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Dibbens
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: John C
authors.initials: JC
authors.lastname: Mulley
mesh_terms: D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D004827:Epilepsy / Q000235:genetics* / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D010865:Pilot Projects; D017384:Sequence Deletion; D016615:Telomere / Q000473:pathology; D055815:Young Adult