|| Checking for direct PDF access through Ovid
We have been recruiting multiplex families into the ‘genetics of familial epilepsy’ study since 2006.Clinicians referred patients with a familial history (typically three or more relatives with epilepsy). We conducted telephone interviews, performed home visits, collected DNA samples, reviewed medical notes, constructed pedigrees and performed epilepsy phenotyping. We directly sequenced candidate genes, performed exome sequencing and functional laboratory experiments where possible.We recruited 110 families and collected DNA samples from 251 affected and 479 unaffected individuals. 36 families have predominantly generalised epilepsy, 27 predominantly focal epilepsy, 23 families have both focal and generalised epilepsy, and 24 families have unclassifiable epilepsy. We identified several specific familial phenotypes including: genetic epilepsy with febrile seizures plus (GEFS+) n=16; familial temporal lobe epilepsy n=9; benign familial neonatal seizures n=2; autosomal dominant lateral temporal lobe epilepsy n=1 and familial cavernomas n=1. Causative mutations were found in genes including GABRG2, KCNQ2, KRIT1, LGI1 and SLC2A1.We identified a monogenetic cause for the epilepsy in 5% of our families. 20% of our unresolved families have individuals with generalised and individuals with focal epilepsy, a finding which has been replicated in other recent studies, suggesting that common genetic mechanisms can cause ‘mixed’ phenotypes.