RESUMO
Primary focal dystonia (PFD) is known to be a clinically and genetically heterogeneous group of movement disorders. To evaluate the frequency of familial focal dystonia in a French population presenting with PFD, we screened 197 patients (150 index cases and 47 affected family members) presenting focal primary dystonia for the GAG deletion in the DYT1 gene and analyzed linkage to the DYT6, DYT7, and DYT13 loci in those who presented a family history. Fourteen families could be recruited and, among them 47 new symptomatic individuals could be identified by clinical examination. A group of 104 patients were without family history and 46 patients (30.7%) were found to have at least one first-degree relative with dystonia. Mean age at onset was significantly later (55.4 +/- 14.0 years) in the blepharospasm group and earlier in patients with writer's cramp (35.8 +/- 14.0 years). The group of patients with family history showed a mean age at onset significantly earlier (39.2 +/- 18.0) than in patients without family history (47.4 +/- 14.4 years). Fourteen families demonstrated an autosomal mode of transmission and five families were studied further for genetic linkage analysis, but no significant linkage to one of the three loci could be observed. Our results illustrate the importance of genetic factors and the clinical heterogeneity of PFD. They indicate the existence of one or several as yet unmapped genes responsible for these diseases.
Assuntos
Proteínas de Transporte/genética , Distúrbios Distônicos/epidemiologia , Distúrbios Distônicos/genética , Desequilíbrio de Ligação , Adulto , Fatores Etários , Idade de Início , Idoso , Blefarospasmo/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 9 , Análise Mutacional de DNA , Distúrbios Distônicos/classificação , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Repetições de TrinucleotídeosRESUMO
Genomic triplication of the alpha-synuclein gene (SNCA) has been reported to cause hereditary early-onset parkinsonism with dementia. These findings prompted us to screen for multiplication of the SNCA locus in nine families in whom parkinsonism segregates as an autosomal dominant trait. One kindred was identified with SNCA duplication by semiquantitative PCR and confirmed by fluorescent in-situ hybridisation analysis in peripheral leucocytes. By contrast with SNCA triplication families, the clinical phenotype of SNCA duplication closely resembles idiopathic Parkinson's disease, which has a late age-of-onset, progresses slowly, and in which neither cognitive decline nor dementia are prominent. These findings suggest a direct relation between SNCA gene dosage and disease progression.
