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.365TA (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.