Genetic linkage study of an autosomal recessive form of juvenile myoclonic epilepsy in a consanguineous Tunisian family

SummaryJuvenile myoclonic epilepsy (JME) is the most common idiopathic generalized epilepsies (IGEs), affecting 12–30% of all epilepsies in medical centers. To date genetic linkage studies have revealed putative loci on different chromosomes, but these findings are still inconclusive about which gene precisely is responsible for the disease. Here, we report the genetic and clinical analysis of a (JME) consanguineous Tunisian family with four affected children out of eight. A genome-wide search was carried out by using the Affymetrix GeneChip Mapping 500K NspI chip. Pairewise logarithm of the odds (LOD) scores were calculated with MERLIN (1.1) assuming an autosomal recessive model, and a complementary homozygous mapping analysis was performed with AutoSNPa software. The genome-wide parametric linkage analysis showed suggestive linkage to chromosome 2q. Interactive visual analysis of SNP data using AutoSNPa revealed two large regions of shared homozygosity by descent on 2q23.3 and on 2q24.1. We decided to sequence the exons of the two genes coding for such proteins located in 2q23.3, CACNB4 and 2q24.1, KCNJ3. No nucleotide variation – comprising the previously reported mutations – was detected.