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| Isabel Alonso |
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Rua do Campo Alegre, 823 - Porto - Portugal
e-mail: ialonso@ibmc.up.pt |
Poster Presentation: |
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| A UNIQUE CACNA1A MISSENSE MUTATION CAUSES PHENOTYPES OF SPINOCEREBELLAR ATAXIA TYPE 6 (SCA6) AND FAMILIAL HEMIPLEGIC MIGRAINE (FHM) IN PATIENTS FROM A LARGE FAMILY. |
| Alonso I.1,2, Tuna A.3, Coelho J.1, Barros J.3, Sequeiros J.1,2, Silveira I.1,2 Coutinho P.4 | |
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Porto - Portugal |
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| Familial hemiplegic migraine (FHM) is a neurological disorder, characterized by episodes of migraine with hemiparesis or other neurological focal deficits, inherited in an autosomal dominant form. FHM can also be associated with fever, confusion, coma or ataxia. Seven different missense mutations in a gene that encodes a subunit of a neuronal calcium channel cause FHM. Mutations disrupting this gene are also involved in episodic ataxia type 2 (EA2), whereas expansion of a CAG repeat causes spinocerebellar ataxia type 6 (SCA6). We ascertained 29 individuals from a four-generation family, comprising 14 patients with multiple and different phenotypes of progressive cerebellar ataxia, hemiplegic migraine, focal neurological deficits and coma triggered by minor head trauma, dominantly inherited. We have (1) assessed CAG repeat size at the SCA6 locus; (2) performed linkage analysis with chromosome 19p markers D19S1150, D19S840 and D19S226 and (3) screened our family for mutations in the CACNA1A gene. Polymorphism detection was performed by PCR amplification, single strand conformational polymorphism (SSCP) analysis and sequencing. Expansions of the CAG repeat were not present in any of these patients. Linkage analysis was performed and showed positive lod scores to chromosome 19p markers. SSCP and sequencing detected a G-to-A substitution in exon 13 of the CACNA1A gene, resulting in an arginine to glutamine change at codon 583, previously described. This mutation is present in all 12 living patients and also in one at-risk individual. In conclusion, the same missense mutation in the CACNA1A gene gives raise to varied clinical syndromes of permanent ataxia, hemiplegic migraine and episodes of focal deficits or coma triggered by minor head trauma.
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