RESUMO
BACKGROUND: Mutations in the spastin gene are the commonest cause of hereditary spastic paraparesis (HSP), accounting for up to 40% of autosomal dominant cases. The phenotype associated with HSP due to mutation in the spastin gene (SPG4) tends to be pure HSP. OBJECTIVE: To characterize in more detail the genetic and phenotypic characteristics of SPG4 by examining a large cohort of patients with HSP. METHODS: The authors identified patients who tested positive for spastin mutation using a direct sequencing approach of all exons. RESULTS: The authors identified spastin mutations in 53 patients. Twenty-seven of the mutations identified were novel. The phenotype in the majority of patients was of pure HSP. In one individual, a complicated phenotype with progressive bulbar dysfunction and respiratory insufficiency was observed. Evidence of lower motor neuron dysfunction in a subgroup of SPG4 patients was identified. The missense changes S44L and P45Q were identified in patients with other spastin mutations and seemed to be exerting a phenotype-modifying effect. CONCLUSION: These findings add to the number of spastin mutations identified and demonstrate the importance of screening the whole gene, given the possibility of double mutations and intragenic modifiers. The identification of the complicated phenotypes has important implications for identifying the phenotype of patients in whom spastin screening should be considered. The presence of lower motor neuron dysfunction in a subgroup of SPG4 patients suggests that the cellular dysfunction in SPG4 extends beyond the axonal projections of upper motor neurons and ascending sensory pathways.
Assuntos
Adenosina Trifosfatases/genética , Mutação , Paraplegia Espástica Hereditária/genética , Paraplegia Espástica Hereditária/fisiopatologia , Adulto , Idoso , Estudos de Coortes , Análise Mutacional de DNA/métodos , Éxons , Feminino , Testes Genéticos , Glutamina/genética , Humanos , Leucina/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , Prolina/genética , Estudos Retrospectivos , Serina/genética , Paraplegia Espástica Hereditária/epidemiologia , Paraplegia Espástica Hereditária/etiologia , Espastina , Reino Unido/epidemiologiaRESUMO
Community-based AIDS research programs were initially federally funded in 1989. Since then, the Terry Beirn Community Programs for Clinical Research on AIDS has mandated that research units develop and maintain community advisory boards to provide advice and communicate community preferences in AIDS research. Seventeen community-based AIDS research units formed community advisory boards (CABs) based on a model developed by the Community Consortium at San Francisco General Hospital. Social workers employed by these AIDS research units surveyed 267 CAB members to ascertain board characteristics and members' perceptions of program activities. Implications for social work and future research are discussed.
