No mutations in CACNA1A and ATP1A2 in probands with common types of migraine

Background: Mutations in CACNA1A, encoding a neuronal calcium channel subunit, and ATP1A2, encoding a catalytic subunit of a sodium-potassium-ATPase, have been found in some families with dominantly inherited hemiplegic migraine. Objective: To determine the prevalence of mutations in these genes in individuals with different migraine syndromes. Design: Prospective screening study. Setting: University outpatient neurology clinic. Subjects: Probands of 19 families with hemiplegic migraine, 7 with basilar migraine, 25 with migraine without aura, and 18 with migraine with aura, as well as 40 unaffected relatives of probands. Interventions: All known exons and flanking introns of CACNA1A and ATP1A2 were subjected to denaturing. Main Outcome Measures: Presence of mutations in CACNA1A and ATP1A2. high-performance liquid chromatography analysis of polymerase chain reaction-amplified genomic DNA. Exons with atypical elution patterns were sequenced by standard techniques. Results: A single mutation (T666M) was found in CACNA1A in a patient with hemiplegic migraine and ataxia. No other mutation was identified in either gene. The frequency of a previously reported intronic insertion in ATP1A2 was not significantly different between patients with migraine and control subjects. Conclusion: These 2 genes are not associated with more common migraine syndromes and are not the most common hemiplegic migraine genes.