RESUMO
OBJECTIVE: Attacks of familial hemiplegic migraine (FHM) are usually associated with transient, completely reversible symptoms. Here, we studied the ATP1A2 FHM2 gene in a young girl with episodes of both very severe and transient neurological symptoms that were triggered by mild head trauma as well as permanent mental retardation. Her family members suffered from hemiplegic and confusional migraine attacks. METHODS: Mutation analysis of the ATP1A2 gene was performed by direct sequencing of all exons and flanking intronic regions, using genomic DNA of the proband. Functional consequences of the mutation were analyzed by cellular survival assays. RESULTS: We identified a novel G615R ATP1A2 mutation in the proband and several of her family members. Functional analysis of mutant Na,K-ATPase in cellular survival assays showed a complete loss-of-function effect. INTERPRETATION: Permanent mental retardation in children may be caused by ATP1A2 mutations.
Assuntos
Deficiência Intelectual/genética , Enxaqueca com Aura/genética , Mutação , ATPase Trocadora de Sódio-Potássio/genética , Arginina/genética , Northern Blotting/métodos , Western Blotting/métodos , Criança , Análise Mutacional de DNA/métodos , Eletroencefalografia/métodos , Feminino , Expressão Gênica/fisiologia , Glicina/genética , Células HeLa , Humanos , Deficiência Intelectual/patologia , Imageamento por Ressonância Magnética/métodos , Enxaqueca com Aura/patologia , Enxaqueca com Aura/fisiopatologia , Mutagênese/fisiologia , Transfecção/métodosRESUMO
A growing interest in genetic research in migraine has resulted in the identification of several chromosomal regions that are involved in migraine. However, the identification of mutations in the genes for familial hemiplegic migraine (FHM) forms the only true molecular genetic knowledge of migraine thus far. The increased number of mutations in the FHM1 (CACNA1A) and the FHM2 (ATP1A2) genes allow studying the relationship between genetic findings in both genes and the clinical features in patients. A wide spectrum of symptoms is seen in patients. Additional cerebellar ataxia and (childhood) epilepsy can occur in FHM1 and FHM2. Functional studies show a dysfunction in ion transport as the key factor in the pathophysiology of (familial hemiplegic) migraine that predict an increased susceptibility to cortical spreading depression--the underlying mechanism of migraine aura.
Assuntos
Transtornos de Enxaqueca/genética , Animais , Canais de Cálcio/genética , Humanos , Camundongos , ATPase Trocadora de Sódio-Potássio/genéticaRESUMO
Twelve familial hemiplegic migraine (FHM) patients (6 with the I1811L mutation in CACNA1A, 3 with M731T mutation in ATP1A2, and 3 without known mutations) and 10 control subjects underwent single-fiber EMG. Mean jitter did not differ significantly between patients and control subjects or among patients. No blocking was found. The results suggest that neuromuscular function is normal in FHM.
Assuntos
Eletromiografia/métodos , Hemiplegia/etiologia , Enxaqueca com Aura/fisiopatologia , Adolescente , Adulto , Substituição de Aminoácidos , Canais de Cálcio/genética , Sobrancelhas , Feminino , Hemiplegia/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Enxaqueca com Aura/complicações , Enxaqueca com Aura/genética , Mutação de Sentido Incorreto , Mutação Puntual , Método Simples-Cego , ATPase Trocadora de Sódio-Potássio/genéticaRESUMO
Alternating hemiplegia of childhood (AHC) is a rare disorder mainly characterised by attacks of hemiplegia and mental retardation. AHC has often been associated with migraine. Previously, we have excluded the involvement of the familial hemiplegic migraine (FHM) CACNA1A gene in four patients with AHC. A second gene for FHM was discovered recently: the ATP1A2 gene on chromosome 1q23, coding for the alpha 2 subunit of Na+,K+-ATPase. We performed a mutation analysis of the ATP1A2 gene in six patients, using direct sequencing, but found no mutations in any of the 23 exons. Other cerebral ion channel genes remain candidate genes for AHC.
Assuntos
Hemiplegia/genética , ATPase Trocadora de Sódio-Potássio/genética , Adolescente , Criança , Análise Mutacional de DNA , Feminino , Humanos , Enxaqueca com Aura/genéticaRESUMO
Familial hemiplegic migraine (FHM) is a rare, autosomal dominant subtype of migraine, associated in half of the families with mutations in the CACNA1A gene located on chromosome 19p13, which encodes the Cav2.1-subunit of brain-specific P/Q-type calcium channels. Recently, mutations in a second gene, ATP1A2 on chromosome 1q23, which encodes a sodium-potassium exchange pump subunit, have been identified. The first functional studies indicate that A TP1A2 FHM mutations result in a loss of function of the pump, leading to an increase in extracellular potassium. This is known to evoke cortical spreading depression, the underlying mechanism of migraine aura.
Assuntos
Canais de Cálcio/genética , Cromossomos Humanos Par 19 , Enxaqueca com Aura/genética , ATPase Trocadora de Sódio-Potássio/genética , Canais de Cálcio Tipo N , Canais de Cálcio Tipo P , Canais de Cálcio Tipo Q , Predisposição Genética para Doença , Humanos , MutaçãoRESUMO
La cefalea en racimos (CR) o "neuralgia de Horton", es un tipo relativamente raro de cefalea que se presenta en forma de ataques y cuya severidad le ha dado el nombre de "dolor de cabeza suicida". Debido a que la CR es una patología bastante desconocida, el paciente puede tardar en ser diagnosticado, especialmente debido a que es raro que un médico lo atienda en el momento mismo del ataque. La CR suele ser confundida con sinusitis, migraña o patología dental. De ahí que los pacientes no reciban el tratamiento adecuado, o lo reciban demasiado tarde. Sin embargo, la CR es fácil de diagnosticar por lo típico del cuadro clínico, y en la mayoría de los casos, también es fácil de tratar. Por ello es importante que esta enfermedad sea reconocida lo antes posible. Los médicos de cabecera pueden jugar un importante papel en el proceso de diagnóstico. Descriptores: Cefalea en racimos, neuralgia de Horton, triptan.