Abstracts

Rationale: The Idiopathic Generalised Epilepsies (IGE) are common seizure disorders with a strong genetic contribution. Despite convincing evidence from twin studies and family studies, the underlying genetic alterations are largely unknown. 15q13.3 microdeletions have previously been implicated in a distinct syndrome of intellectual disability and epilepsy. As submicroscopic structural genetic variation is increasingly recognised as a source of genetic morbidity in complex genetic disorders, this study aimed to explore a potential role for 15q13.3 microdeletions in common IGE syndromes, a chromosomal region encompassing the alpha-7 subunit gene of the nicotinergic acetylcholine receptor (CHRNA7). Methods: 709 patients with IGE and 1203 controls were genotyped with the Affymetrix Genome-Wide Human SNP Array 6.0 and analysis of copy number variation was performed using the Affymetrix Genotyping Console 2.0 algorithm. Copy number segment files in cases and controls were inspected for deletions of the chromosomal region 15q13.3. Deletions of 15q13.3 spanning the CHRNA7 gene were confirmed using high-resolution oligonucleotide array mapping. Results: Microdeletions of 15q13.3 including the CHRNA7 gene were identified in 7/709 patients with IGE, but were not detected in controls. Associated phenotypes included Childhood Absence Epilepsy (3/7), Juvenile Absence Epilepsy (2/7) and Juvenile Myoclonic Epilepsy (2/7). The size of the deletions ranged from 1,5 MB to 3,6 MB. Conclusions: 15q13.3 microdeletions spanning the CHRNA7 gene were found in up to 1% of all cases with Idiopathic Generalised Epilepsy and may predispose to various IGE subsyndromes. Our findings expand the phenotypic spectrum of 15q13.3 microdeletions from symptomatic epilepsies with intellectual disability to common idiopathic epilepsies, emphasising the importance of structural genetic variation in seizure disorders.