SLC1A3 gene mutation analysis in migraine with aura

Migraine is a common disorder, characterized by recurrent disabling attacks of headache associated with nausea, vomiting, photophobia and phonophobia and, in a five of patients, neurological aura symptoms (migraine with aura). Many migraine researchers believe that migraneous brains are hyperexitable and some triggering factors can give rise to cortical spreading depression (CSD) and neurogenic inflammation, and finally to migraine headache. Cortical spreading depression (CSD) is well established as the underlying mechanism for the migraine aura, and findings based on the animal experiments show that it might also trigger the headache phase of migraine attacks by activating the trigeminovascular system. The rare Mendelian form of migraine FHM is the most successful model for the identification of migraine associated cellular mechanisms. Three genes ?two ion-channel genes and one encoding an ATP exchanger? have been found to underlie FHM. These mutations probably contribute to hyperexcitability of neurons by leading to either an increased release or an inefficient clearing of synaptic glutamate.The gene encoding EAAT- 1 which trasports exitatory aminoacid played a role in glutamate transporting into the cells. Therefore we have investigated SLCIA3 gene mutations in migraine patients with aura.Our studies were conducted with 14 migraine patients with aura and 10 healthy control subjects of different family, and they have been analyzed for mutations in all exon/intron regions. We have found 6 new gene variants (IVS2.+28-29insA, IVS4+17C>T, Phe389Phe(1167C>T), 3?UTR 33+ G>A, 3?UTR 515+A>C). IVS2.+28-29, IVS+17C>T, Phe389Phe(1167C>T gene variants have only been found in three patients but not in healthy subjects, while 3?UTR 33+ G>A, 3?UTR 515+A>C gene variants have been found in both patients and control subjects. Moreover, Glu219Asp(657G>C) gene variant encountered only in three patients, along with IVS8+22C>T gene variant found in seven patients and three healthy control subjects, are considered as polymorphism in the related literature . Among two patients, some clinical features have been evaluated as being different from the others. The patient exhibiting IVS2.+28-29insA gene variant had both visual and somatosensorial aura symptoms. Moreover this patient had episodic vertigo and unsteadiness attacks. The patient having IVS4+17C>T gene variant described vertigo attacks and motion sickness in personal history and this was different from the other patients. Our study was conducted with limited number of patients, but since this study is first among the related literature, the results bear hope to reveal the role of these gene mutations in migraine pathogenesis. However we will require new functional and polymorphism studies for a better understanding of the effects of gene mutations on migraine pathogenesis