Mutation analysis of the CACNA1A calcium channel subunit gene in 27 patients with sporadic hemiplegic migraine.
Abstract:Arch Neurol. 2002 Jun;59(6):1016-1018 Background: Familial hemiplegic migraine is a rare autosomal dominant subtype of migraine with aura that in half of the families is caused by mutations in the CACNA1A gene on chromosome 19p13. In sporadic hemiplegic migraine (SHM), that is, hemiplegic migraine without affected family members, the contribution of the CACNA1A gene is unknown. Objective: To investigate the involvement of the CACNA1A calcium channel subunit gene in SHM. Methods: We screened 27 patients with SHM for mutations in the CACNA1A gene by a combination of single-strand conformational polymorphism analysis and sequence analysis. Results: One patient with SHM also had ataxia, nystagmus, and cerebellar atrophy on computed tomography and carried a T666M mutation. Another patient with SHM who had no cerebellar signs carried an R583Q mutation. No mutations or interictal neurological abnormalities were found in the remaining 25 patients with SHM. Conclusions: Most patients with SHM do not have a CACNA1A mutation. The results of this study, combined with the findings reported in the literature, show that the presence of cerebellar symptoms in addition to the hemiplegic attacks increases the chance of finding a CACNA1A mutation. In addition, to our knowledge, we have found a first patient with SHM without cerebellar signs with a mutation. Comment: The story on calcium channelopathies and neurologic disorders becomes ever more complex, as multiple neurologic disorders appear linked to varying forms of calcium-channel mutations. Professor Ferrari has described links to cerebellar disorders, to a peculiar and severe response to head trauma, and to epilepsy, as well as to familial hemiplegic migraine. Now his group finds that the most frequently found calcium channelopathy mutations are not found in most patients with spontaneous hemiplegic migraine. Does this just mean that other mutations, not yet described, cause a common phenotypic expression? Or are there multiple causes for the hemiplegic migraine syndrome, and not all of them due to calcium channelopathies? SJT
Document Type: Research Article
Publication date: 2003-03-01