Epilepsy as part of the phenotype associated with ATP1A2 mutations

Epilepsia. 2008 Mar;49(3):500-8. doi: 10.1111/j.1528-1167.2007.01415.x. Epub 2007 Nov 19.

Abstract

Purpose: Mutations in the ATP1A2 gene have been described in families with familial hemiplegic migraine (FHM). FHM is a variant of migraine with aura characterized by the occurrence of hemiplegia during the aura. Within several FHM families, some patients also had epileptic seizures. In this study we tested the hypothesis that mutations in ATP1A2 may be common in patients presenting with epilepsy and migraine.

Methods: We selected 20 families with epilepsy and migraine and performed mutation analysis of ATP1A2 in the probands by direct sequencing of all exons and splice-site junctions.

Results: Novel ATP1A2 mutations were found in two of the 20 families (10%). The p.Gly900Arg mutation was present in a family with epilepsy and FHM, and the p.Cys702Tyr mutation occurred in a family with occipitotemporal epilepsy and migraine with and without visual aura. In the two families together, six mutation carriers had the combination of epilepsy and migraine, two had only epilepsy, and six had only migraine.

Discussion: This study shows that a history of migraine and a family history of both epilepsy and migraine should be obtained in all patients presenting with epilepsy in the epilepsy clinic. It may be worthwhile to screen patients with a combination of epilepsy and migraine and a positive family history of either migraine or epilepsy for mutations in the ATP1A2 gene.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Amino Acid Sequence
  • Belgium / epidemiology
  • Comorbidity
  • DNA Mutational Analysis
  • Epilepsy / epidemiology
  • Epilepsy / genetics*
  • Exons / genetics
  • Family
  • Female
  • Gene Frequency / genetics
  • Humans
  • Male
  • Middle Aged
  • Migraine with Aura / epidemiology
  • Migraine with Aura / genetics*
  • Mutation / genetics*
  • Pedigree
  • Phenotype
  • RNA Splice Sites / genetics
  • Sodium-Potassium-Exchanging ATPase / genetics*
  • White People / genetics

Substances

  • RNA Splice Sites
  • ATP1A2 protein, human
  • Sodium-Potassium-Exchanging ATPase