A novel loss-of-function LGi1 mutation linked to autosomal dominant lateral temporal epilepsy

Background: Mutations responsible for autosomal dominant lateral temporal epilepsy have been found in the leucine-rich, glioma-inactivated 1 (LGI1) gene. Objectives: To describe the clinical and genetic findings in a family with autosomal dominant lateral temporal epilepsy and to determine the functional effects of a novel LGI1 mutation in culture cells. Design: Clinical, genetic, and functional investigations. Setting: University hospital and laboratory. Patients: An Italian family with autosomal dominant lateral temporal epilepsy. Main Outcome Measure: Mutation analysis. Results: A novel LGI1 mutation, c.365T>A (Ile122Lys), segregating with the disease was identified. The mutant Lgi1 protein was not secreted by culture cells. Conclusion: Our data provide further evidence that mutations in LGI1 hamper secretion of the Lgi1 protein, thereby precluding its normal function.