A novel loss-of-function LGI1 mutation linked to autosomal dominant lateral temporal epilepsy

Arch Neurol. 2008 Jul;65(7):939-42. doi: 10.1001/archneur.65.7.939.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Line
  • DNA Mutational Analysis / methods
  • Epilepsy, Temporal Lobe / diagnosis
  • Epilepsy, Temporal Lobe / genetics*
  • Epilepsy, Temporal Lobe / physiopathology*
  • Female
  • Genes, Dominant / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree
  • Proteins / genetics*
  • Proteins / metabolism

Substances

  • Intracellular Signaling Peptides and Proteins
  • LGI1 protein, human
  • Proteins