Update on the genetics of migraine.
The field of migraine genetics has seen an explosion of information over the last year. In a recent breakthrough, missense mutations in a chromosome 1q23 gene, ATP1A2, encoding a Na+, K+-ATPase, have been identified in four distinct pedigrees with a rare form of familial hemiplegic migraine (FHM). ATP1A2 is expressed in the brain, like the voltage gated calcium channel gene, CACNA1A, previously identified as the first hemiplegic migraine gene (FHM1). The shared hemiplegic migraine phenotype of mutations in ATP1A2 and CACNA1A raises the possibility that they coordinately regulate ion homeostasis that determines susceptibility to the initiation of both migraine aura and the pain phase of migraine. For the more common and genetically complex forms of migraine, genome-wide screens have identified several new loci on 4q24, 6p12.2-21.1, 11q24, and 14q21.2-q22.3, suggesting additional migraine genes in these regions. In addition, a recent large case-control association study has linked single nucleotide polymorphisms in the insulin receptor/INSR gene with migraine. However, these polymorphisms do not result in detectable changes in receptor function. The continuing genetic identification of key proteins involved in migraine will refine our understanding of this common and sometimes debilitating disorder, which can strike during the most productive years of a person's life. Given the co-morbidity of migraine with depression and bipolar disorder, our knowledge of the causes of migraine may also contribute to our understanding of these disorders.
Estevez
Miguel
M
Department of Neurology, Veterans Administration Hospital and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. m_estevez@yahoo.com
Gardner
Kathy L
KL
D000818:Animals; D015220:Calcium Channels / Q000235:genetics; D002887:Chromosomes, Human, Pair 18; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008881:Migraine Disorders / Q000209:etiology / Q000235:genetics*; D020325:Migraine with Aura / Q000235:genetics; D008957:Models, Genetic; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide
D015220:Calcium Channels