RESUMO
Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura with an autosomal dominant pattern of inheritance. Six FHM families underwent extensive clinical and genetic investigation. The authors identified a novel ATP1A2 mutation (E700K) in three patients from one family. In the patients, attacks were triggered by several factors including minor head trauma. In one subject a 3-day coma developed after a cerebral angiography. Overall, the phenotype of the patients closely resembles that of previously reported cases of FHM type II. The E700K variant might be regarded as the cause of the disease in this family, but this was not tested functionally.
Assuntos
Enxaqueca com Aura/genética , ATPase Trocadora de Sódio-Potássio/genética , Idoso , Sequência de Aminoácidos , Animais , Sequência de Bases , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , Linhagem , Reação em Cadeia da Polimerase , RatosRESUMO
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset familial disease with prominent myelinated fibers in the optic fundus. ARSACS is frequent in the Charlevoix-Saguenay region of Quebec but rare elsewhere. Mutations in SACS, encoding sacsin, a protein of unknown function, are associated with ARSACS. The authors identified three new SACS mutations in two Italian patients whose phenotype closely matches that of Quebec cases, but without retinal striation.
Assuntos
Ataxia/genética , Genes Recessivos/genética , Proteínas de Choque Térmico/genética , Espasticidade Muscular/genética , Mutação , Adulto , Idade de Início , Ataxia/complicações , Ataxia/diagnóstico , Cerebelo/patologia , Consanguinidade , Análise Mutacional de DNA , Progressão da Doença , Triagem de Portadores Genéticos , Haplótipos , Homozigoto , Humanos , Itália , Imageamento por Ressonância Magnética , Masculino , Dados de Sequência Molecular , Espasticidade Muscular/complicações , Espasticidade Muscular/diagnóstico , FenótipoRESUMO
The authors report on a novel frameshift mutation (c.1688insA) in the SPG3A gene resulting in premature translation termination of the gene product atlastin. These data add a new variant to the second disease gene in autosomal dominant hereditary spastic paraplegia (ADHSP) and lend definitive support to its causative role. By combining direct testing of SPAST and SPG3A, at least 50% of ADHSP families can now receive appropriate genetic diagnosis.
