Migraine With Aura, Susceptibility To, 7

For a phenotypic description and discussion of genetic heterogeneity of migraine headaches, see MGR1 (157300).

Migraine is the most common type of chronic episodic headache. Population-based family studies had suggested a strong genetic predisposition to migraine, especially migraine with aura (MA). GABA-A receptors (see 137192) and their modulator sites seem to be involved in the pathophysiologic events that underlie migraine. Russo et al. (2005) reported clinical and molecular data from 10 families with MA, in which MA segregated as an autosomal dominant trait and presented with homogeneous clinical features. After excluding linkage with the known candidate loci, Russo et al. (2005) used a functional candidate approach and genotyped the 10 families with markers from the 15q11-q13 genomic region, which contains genes encoding GABA-A receptor subunits. Using a parametric 2-point linkage analysis, evidence of linkage was obtained for GABRB3 (137192) located at 15q11.2-q12 with a maximum lod score of 5.56 at a recombination fraction of 0.001. Linkage was supported by multipoint analysis with a maximum lod score of 6.54 between markers D15S113 and D15S1019. The critical region spans 3.6 Mb. Russo et al. (2005) concluded that their results provided the basis for further investigation of the hypothesized relationship between a GABA-A receptor dysfunction and migraine.