Genetic Analysis of Epilepsy in Consanguineous Families

Abstract

Epilepsy is a neurological disorder, which is also referred as seizure disorder. It is mainly characterized by recurrent seizures and is classified into different types depending on the clinical features and the type of seizure presented by the respective patient. Approximately 168 genes have been identified in patients with isolated epilepsy. Out of these, 90 genes (53%) are involved in causing autosomal dominant epilepsy and 62 genes (32%) are known for autosomal recessive epilepsy. However, mutations in some genes (SCN1A, KCNQ2, STXBP1, KCNQ3, DEPDC5, SCN2A, PRRT2, DEPDC5) have been identified in both autosomal dominant and recessive epilepsy. The clinical features of patients from five families included the presentation of tonic clonic seizures. All five families showed autosomal recessive inheritance of epilepsy, and the presented clinical features resemble Dravet syndrome, which is mainly caused by mutation in SCN1A gene. Blood was drawn from all family members but only one affected member from each family was selected for Sanger sequencing of SCN1A gene. Five exons of SCN1A gene were selected including exon 5, 15, 21, 25, and 26. The analysis of Sanger sequencing data detected a homozygous polymorphism g.19189-19190insG in family B which lies in the intron 5, one variant of unknown significance i.e., g.82579A>G in family B and D which lies in 3’untranslated region (3’UTR) of exon 26, and a homozygous polymorphism g.64092_64093isnA in intron 21 of family D. The g.82579A>G is identified in two families (B, D) in the homozygous state and is predicted as disease causing by mutation taster. However, additional studies are required to explore the functional effect of this variant. No variant was identified in family A, C and E. In conclusion, a potential variant was identified in two families, but further research will be required to find the disease-causing variants in the remaining three families. Keywords: Epilepsy, seizures, Dravet syndrome, SCN1A