English abstract
Introduction: Epilepsy is a common, heterogeneous neurological condition whose genetics is only started to be unravelled. Identification of the genes related to epilepsy will increase biological interpretation of the mutated gene therefore gives a better understanding of the origin of the patient's phenotype and gives option for the treatment. Exome sequencing along with homozygosity mapping is a powerful tool which helps to uncover the possible variants in the shared homozygous region among the affected individuals. This study is focused to uncover the genetic basis of autosomal recessive epilepsies in a subset of Omani families. Methods: Three consanguineous Omani families with three apparently different autosomal form of recessive epilepsies were enrolled in the study. The families were diagnosed with Epileptic encephalopathy, epilepsy with secondary generalized seizures and progressive myoclonic epilepsy (PME) respectively. Exome sequencing was performed and the obtained variants were filtered using various filtering strategies. The final variants were biologically interpreted to understand the basis of the phenotype. Pathogenicity was tested using computational tools. The strongest candidate gene was selected and sequenced to confirm nature of variation and for segregation analysis. Results: Variation in PSAP gene was identified in family 3 which as labelled as PME. Co-segregation analysis and functional studies such as mRNA splicing analysis and immunofluorescence microscopy are to be done. Variations in XBPI and ALDH3B1 were identified in the other families, which requires further investigations before pathogenicity can be confirmed. Conclusion: Variation in PSAP was found to be the strongest candidate gene whereas confirmation of variation in XBPI and ALDH3B1 requires more clinical details and investigations
