title: A new susceptibility locus for migraine with aura in the 15q11-q13 genomic region containing three GABA-A receptor genes.
abstract: Migraine is the most common type of chronic episodic headache. Several population-based family studies have suggested a strong genetic predisposition to migraine, especially migraine with aura (MA). Although several susceptibility loci have been identified, none of the numerous studies performed to date have led to the identification of a gene responsible for the more common forms of migraine. GABA-A receptors and their modulator sites seem to be involved in the pathophysiological events that underlie migraine. We report on clinical and molecular data from a total of 10 families with MA, in which MA segregates as an autosomal dominant trait and presents with homogeneous clinical features. After excluding linkage with the known candidate loci, we used a functional candidate approach and genotyped these families with markers from the 15q11-q13 genomic region, which contains the genes encoding GABA-A receptor subunits. Evidence of linkage was obtained with a parametric two-point linkage analysis (maximum LOD score of 5.56 at a recombination fraction of 0.001 for marker GABRB3) and was supported by multipoint analysis (maximum LOD score of 6.54 between markers D15S113 and D15S1019). The critical region spanned 3.6 Mb. These results provide the basis for further investigation of the hypothesized relationship between a GABA-A receptor dysfunction and migraine.
authors.affiliation: Institute of Medical Genetics, Catholic University, Rome, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Russo
authors.forename: Paolo
authors.initials: P
authors.lastname: Mariotti
authors.forename: Eugenio
authors.initials: E
authors.lastname: Sangiorgi
authors.forename: Tiziana
authors.initials: T
authors.lastname: Giordano
authors.forename: Iolanda
authors.initials: I
authors.lastname: Ricci
authors.forename: Francesca
authors.initials: F
authors.lastname: Lupi
authors.forename: Rossella
authors.initials: R
authors.lastname: Chiera
authors.forename: Francesco
authors.initials: F
authors.lastname: Guzzetta
authors.forename: Giovanni
authors.initials: G
authors.lastname: Neri
authors.forename: Fiorella
authors.initials: F
authors.lastname: Gurrieri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020325:Migraine with Aura / Q000235:genetics*; D010375:Pedigree; D011963:Receptors, GABA-A / Q000235:genetics*
chemical_list: D011963:Receptors, GABA-A