First case of compound heterozygosity in Na,K-ATPase gene ATP1A2 in familial hemiplegic migraine

Eur J Hum Genet. 2007 Aug;15(8):884-8. doi: 10.1038/sj.ejhg.5201841. Epub 2007 May 2.


Familial hemiplegic migraine (FHM) is a rare autosomal-dominant subtype of migraine with aura, associated with hemiparesis during the aura. Here we describe a unique FHM family in which two novel allelic missense mutations in the Na,K-ATPase gene ATP1A2 segregate in the proband with hemiplegic migraine. Both mutations show reduced penetrance in family members of the proband. Cellular survival assays revealed Na,K-ATPase dysfunction for both ATP1A2 mutants, indicating that both mutations are disease causative. This is the first case of compound heterozygosity for any of the known FHM genes.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Child
  • Female
  • Heterozygote*
  • Humans
  • Male
  • Migraine with Aura / genetics*
  • Molecular Sequence Data
  • Pedigree
  • Sodium-Potassium-Exchanging ATPase / genetics*


  • ATP1A2 protein, human
  • Sodium-Potassium-Exchanging ATPase