| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 10q25.3 | {Migraine, with or without aura, susceptibility to, 13} | 613656 | Autosomal dominant | 3 | KCNK18 | 613655 |
A number sign (#) is used with this entry because of evidence that susceptibility to migraine with aura-13 (MGR13) is conferred by heterozygous mutation in the KCNK18 gene (613655) on chromosome 10q25. One such family has been reported.
Lafreniere et al. (2010) reported a large 4-generation family in which migraine with aura was transmitted in an autosomal dominant pattern. The female proband had onset in her early teens of migraine headaches with visual aura. The visual aura was characterized by bilateral slowly enlarging scotoma with a scintillating edge, typically lasting 20 to 30 minutes, and followed by a throbbing lateralized or holocranial headache. The headache had a duration of 24 to 48 hours and was associated with sensitivity to lights, sounds, and smells, as well as nausea and occasional vomiting. Headaches also occurred in isolation without a preceding aura. Triggers included fatigue, alcohol, and bright lights. There was no clear association with the menstrual cycle, but the migraines were less frequent after menopause. Seven additional affected individuals in the family described similar migraine episodes with aura.
In affected members of a family with autosomal dominant transmission of migraine with aura, Lafreniere et al. (2010) identified a heterozygous truncating mutation in the KCNK18 gene (613655.0001), which encodes the TWIK-related spinal cord K+ (TRESK) channel. The gene was chosen for direct sequencing by a candidate gene approach method, since two-pore domain (K2P) potassium channels are associated with neuronal excitability and modulation of pain. The mutation segregated only with the 8 affected family members. The proband in this family was the only 1 of 621 migraine probands sequenced who was found to have a mutation in KCNK18, suggesting that KCNK18 mutations are a rare cause of this disorder.
Lafreniere, R. G., Cader, M. Z., Poulin, J.-F., Andres-Enguix, I., Simoneau, M., Gupta, N., Boisvert, K., Lafreniere, F., McLaughlan, S., Dube, M.-P., Marcinkiewicz, M. M., Ramagopalan, S., Ansorge, O., Brais, B., Sequeiros, J., Pereira-Monteiro, J. M., Griffiths, L. R., Tucker, S. J., Ebers, G., Rouleau, G. A. A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura. Nature Med. 16: 1157-1160, 2010. [PubMed: 20871611] [Full Text: https://doi.org/10.1038/nm.2216]