RESUMO
BACKGROUND AND PURPOSE: Migraine is a common neurological disabling disorder, and anomalies of vascular function have been implied in its pathophysiology. Several findings point to a possible role of the endothelin receptor type A (EDNRA) in migraine. We aim to assess the involvement of endothelin receptor type A (EDNRA) in migraine susceptibility in a sample of Portuguese migraineurs. METHODS: Three tagging SNPs (rs702757, rs5333 and rs5335) were analysed in 188 cases - 111 without aura (MO) and 77 with aura (MA) - and 287 controls. A multivariable logistic regression was performed, including the three SNPs, adjusted for gender. Allelic and haplotypic frequencies were compared between cases and controls. Significant or promising results were confirmed by a multifactor dimensionality reduction analysis (MDR). RESULTS: We found a nominal association for the rs702757 T-allele [odds ratio (OR) = 1.44, 95% confidence intervals (CI): 1.05-1.99] and for the TT-genotype (OR = 2.34, 95% CI: 1.12-4.90) for MO, that do not remain significant after multiple test correction. A trend towards an increased risk for MA regarding the C-allele of rs5333 was also found. However, an additional MDR analysis was performed, and highly significant results were found for the two SNPs. The T-C-G haplotype (rs702757-rs5333-rs5335) was found to be significantly overrepresented in the MO subgroup, even after permutation was performed. CONCLUSIONS: Our results show additional findings for a role of EDNRA as a susceptibility factor for MO, although we cannot exclude the involvement of this gene in MA susceptibility in our population. Our study also emphasizes the need for replication of association findings in different populations.
Assuntos
Predisposição Genética para Doença/genética , Enxaqueca sem Aura/genética , Receptor de Endotelina A/genética , Adolescente , Adulto , Idade de Início , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Portugal , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto JovemRESUMO
Almost all mutations in the SCN1A gene, encoding the alpha(1) subunit of neuronal voltage-gated Na(V)1.1 sodium channels, are associated with severe childhood epilepsy. Recently, two mutations were identified in patients with pure familial hemiplegic migraine (FHM). Here, we identified a novel SCN1A L263V mutation in a Portuguese family with partly co-segregating hemiplegic migraine and epilepsy. The L263V mutation segregated in five FHM patients, three of whom also had epileptic attacks, occurring independently from their hemiplegic migraine attacks. L263V is the first SCN1A mutation associated with FHM and co-occurring epilepsy in multiple mutation carriers, and is the clearest molecular link between migraine and epilepsy thus far. The results extend the clinical spectrum associated with SCN1A mutations and further strengthen the molecular evidence that FHM and epilepsy share, at least in part, similar molecular pathways.
Assuntos
Epilepsia/complicações , Epilepsia/genética , Enxaqueca com Aura/complicações , Enxaqueca com Aura/genética , Proteínas do Tecido Nervoso/genética , Canais de Sódio/genética , Adolescente , Adulto , Idade de Início , Sequência de Aminoácidos , Animais , Criança , Feminino , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Canal de Sódio Disparado por Voltagem NAV1.1 , Linhagem , Reação em Cadeia da Polimerase , Homologia de Sequência de AminoácidosRESUMO
Mutations in the ATP1A2 gene, encoding the alpha2-subunit of the Na+,K+-ATPase, are associated with familial hemiplegic migraine type 2. The majority of ATP1A2 mutations were reported in patients with hemiplegic migraine without any additional neurological findings. Here, we report on two novel ATP1A2 mutations that were identified in two Portuguese probands with hemiplegic migraine and interesting additional clinical features. The proband's of family 1 (with a V362E mutation) had mood alterations, classified as a borderline personality. The proband in family 2 (with a P796S mutation) had mild mental impairment, in addition to hemiplegic migraine; more severe mental retardation was observed in his brother, who also had hemiplegic migraine and carried the same mutation. Cell-survival assays clearly showed abnormal functioning of mutant Na+,K+-ATPase, indicating that both ATP1A2 mutants are disease causing. Additionally, our results suggest a possible causal relationship of the ATP1A2 mutations with the complex clinical phenotypes observed in the probands.
Assuntos
Deficiência Intelectual/genética , Enxaqueca com Aura/genética , Transtornos do Humor/genética , Mutação de Sentido Incorreto , ATPase Trocadora de Sódio-Potássio/genética , Adolescente , Adulto , Saúde da Família , Humanos , Masculino , Linhagem , Fenótipo , PortugalRESUMO
A type of headache associated with altitude variations in airplane travellers is increasingly reported and has recently become a subject of debate for experts. We present a patient with headache related to altitude variations in two different settings: airplane and mountain descent, suggesting that different kinds of triggers for pressure variation can cause the same type of pain.