Abstract (EN):
Introduction: Familial Hemiplegic Migraine (FHM) is an autosomal dominant subtype of migraine with aura, with hemiparesis characterizing the attacks. Genetic studies in families of different origins have contributed for the localization of loci and genes responsible for the disease. The majority of the families affected with FHM and additional cerebellar signs that are linked to 19p13 locus (FHM1) show mutations in CACNA1A gene. On the other hand, families with pure FHM linked to 1q23 locus (FHM2) present genetic variants in ATP1A2 gene. Recently, a mutation in SCN1A gene was associated with FHM (FHM3), supporting the hypothesis that alterations in the ionic homeostasis contribute for the pathogenic mechanism of the disease. For FHM1 several recurrent mutations have been described and allow a more accurate genotype-phenotype correlation. However, for the remaining FHM types only the study of additional families and/or finding recurrent mutations will allow to understand the true importance of each gene for migraine clinical expression. Objective: This work aimed to study the involvement of ATP1A2 gene in a Portuguese family with pure FHM. Patients and Methods: Genetic markers located in the 1q23 region were genotyped for some family members and haplotype analysis was established. Scanning for mutations in the ATP1A2 gene was performed by direct sequencing, using genomic DNA of one patient of the family. Results: We identified the M731T missense mutation, previously described in a Dutch family with pure FHM, which is responsible for the disease in our family. Comparison of haplotypes of both the Dutch and the Portuguese family with the M731T mutation indicated that the mutation is recurrent rather than result of a common founder effect. Conclusion: The association of M731T mutation with pure FHM suggests the preferential study of this mutation in novel FHM Portuguese cases presenting this phenotype.
Language:
Portuguese
Type (Professor's evaluation):
Scientific