Abstracts

Rationale: Familial adult-onset myoclonic epilepsy (FAME) with tremulous movements and generalized seizures has been described in the late 80s. Following this initial report, about 60 families with similar clinical manifestations have been reported under various names (FCMTE, ADCME, BAFME, FAME, Crt Tr, FCMT, FEME, FMEA, THE and FCTE) (Sharifi et al., 2012). Although those syndromes have minor differences, this combination of cortical tremor, myoclonus and epilepsy creates a distinct syndrome (Zara et al., 2005). In some cases, a slow cognitive decline has been observed (Crompton et al., 2012). In contrast with the majority of myoclonic epilepsies, the disease is inherited in an autosomal dominant fashion and the onset is in the early adulthood. To date, positive linkage was established at three distinct loci (8q23.3-8q24.11; 2p11.1-2q12.2; 5p15) but no causal gene has been identified. Methods: We studied two families with FAME by using massive parallel sequencing. Genomic DNA was fragmented and enriched with SureSelect Human All Exon 50 MB kit (Agilent Technologies, CA, USA), and the prepared library was sequenced with 100 bp paired-end reads on the Hiseq 2000 (Illumina, CA, USA). The reads were mapped against the human genome (hg19) with Burrows-Wheeler Aligner (BWA) (version 0.5.8c) and only reads with unique mapping location were kept for downstream analysis. The software SAMtools (version 0.0.11) was used for the calling of single nucleotide variations (SNV), small insertions and small deletions (Indels). dbSNP 132 was used to exclude common variants from the general population. Results: The first kindred is a 2 generations family of Spanish origin and has 3 affected individuals whereas the second family is of French-Canadian origin and has 9 affected individuals over 6 generations. Bioinformatic filtering for coding and splice variants located on chromosomes 2, 5 and 8 led us to detect 79 different variants shared between the two affected individuals from the Spanish family. Validation by Sanger sequencing of several candidate genes has confirmed 8 shared variants. Analyses of the FC family is currently underway. Conclusions: In the past years, massive parallel sequencing techniques have proven to be very effective in the identification of disease causing gene. We report exome sequencing on two autosomal dominant families with FAME from European and French Canadian ancestry with putative candidate genes for the disease.