Caracterização fenotípica e genotípica de parkinsonismo e distonia familiares no ambulatório de distúrbios de movimento do Hospital das Clínicas da Universidade Federal de Minas Gerais

• Ano de defesa: 2008
• Autor(a) principal: Sarah Teixeira Camargos
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Distonia de início precoce; Avaliação fenotípica; Parkinsonismo; Avaliação genotípica; Doença de Parkinson; Avaliação; Genótipo; Distúrbios distônicos; Clínica Médica; Fenótipo
• Link de acesso: http://hdl.handle.net/1843/ECJS-7GJGLB

The aim of this study was to characterize phenotipically and genotipically patients with early onset and familiar parkinsonism and dystonia. During the period of june 2005 through june 2006, 575 patients were assisted at Movement Disorder Clinic, Minas Gerais Federal University. From all, 39% filled criteria for parkinsonism and 33% for dystonia. We selected eight familiar Parkinson disease patients, 45 earlyonset Parkinson disease patients (EOPD), 11 dystonia and parkinsonism patients, seven dopa responsive dystonia patients, four patients with diagnosis of neurodegeneration with brain iron accumulation and 21 patients with familiar dystonia and early onset dystonia. Accordingly with the phenotype, we studied the known genes PRKN, PINK1, LRRK2, SNCA, GCH1, PANK2, DYT1, DYT12. Genedosage was performed for the exons of PRKN and PINK1. Hereditary causes were identified in 18.8% of patients with parkinsonism and dystonia. We described new mutations in PINK1 gene (del exon 7), LRRK2 (Q923H) and CGH1 (T209P). We have found the described mutations in PRKN (W54R in compound heterozygous with V3I; 255Adel in compound heterozygous with T240M, P253R in compound heterozygous with exon 5 duplication, 255Adel single mutation andT240M single mutation), GCH1 (M211V e K224R) and PANK2 (N294I). Patients with early onset Parkinson disease and patients with autosomal recessive inheritance (negative for known mutations) were selected for Whole Genomic Association Study. We failed to find any SNP with significant statistical association in parkinsonian patients when compared with controls. We also failed to find structural association (deletion or duplication) in a region not previously described in healthy controls. A common homozygous track was found in two non correlatedand consanguineous families with dystonia and parkinsonism. This was located in the chromosome 2 in a region comprising 1.2Mb. The codifying exons from the 12 genes from region were sequenced and we found a mutation segregating disease at PRKA gene(P222L). The gene codifies a protein kinase, interferon-inducible double-stranded RNA-dependent activator. PRKA activates a latent PKR in case of cellular stress. We describe a new gene related to dystonia; the first with autosomal recessive inheritance, nominated DYT16. Non hereditary causes(environmental), not tested genes or not described genes might participate of the disease pathology in the cases we didnt find out the cause.