Migraine Genetics: Part II

Authors


  • Conflict of Interest: The authors report no conflict of interest.
  • This review article is based upon a chapter to be published in Dodick, D. and Silberstein, S. (ed.) Migraine, Second Edition. The book is to be published by Oxford University Press. Publication of this review article is with support from Oxford University Press.

Address all correspondence to D.W. Dodick, Department of Neurology, Mayo Clinic, 5777 E. Mayo Blvd., Phoenix, AZ 85054, USA.

Abstract

Migraine clusters in families and is considered to be a strongly heritable disorder. Hemiplegic migraine is a rare subtype of migraine with aura that may occur as a familial or a sporadic condition. Three genes have been identified studying families with familial hemiplegic migraine (FHM). The first FHM gene that was identified is CACNA1A. A second gene, FHM2, has been mapped to chromosome 1 q 21-23. The defect is a new mutation in the α2 subunit of the Na/K pump (ATP1A2). A third gene (FHM3) has been linked to chromosome 2q24. It is due to a missense mutation in gene SCN1A (Gln1489Lys), which encodes an α1 subunit of a neuronal voltage-gated Na+ channel. Genome-wide association studies have identified many non-coding variants associated with common diseases and traits, like migraine. These variants are concentrated in regulatory DNA marked by deoxyribonuclease I hypersensitive sites. A role has been suggested for the two-pore domain potassium channel, TWIK-related spinal cord potassium channel. TWIK-related spinal cord potassium channel is involved in migraine by screening the KCNK18 gene in subjects diagnosed with migraine.

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