RESUMO
Parkinson's disease is the second most frequent neurodegenerative disorder in the world, affecting 1-2% of individuals over the age of 65. The etiology of Parkinson's disease is complex, with the involvement of gene-environment interactions. Although it is considered a disease of late manifestation, early-onset forms of parkinsonism contribute to 5-10% of all cases. In the present study, we screened mutations in coding regions of PARK2 and PINK1 genes in 136 unrelated Brazilian patients with early-onset Parkinson's disease through automatic sequencing. We identified six missense variants in PARK2 gene: one known pathogenic mutation, two variants of uncertain role, and three nonpathogenic changes. No pathogenic mutation was identified in PINK1 gene, only benign polymorphisms. All putative pathogenic variants found in this study were in heterozygous state. Our data show that PARK2 point mutations are more common in Brazilian early-onset Parkinson's disease patients (2.9%) than PINK1 missense variants (0%), corroborating other studies worldwide.
Assuntos
Doença de Parkinson/genética , Proteínas Quinases/genética , Ubiquitina-Proteína Ligases/genética , Adulto , Idade de Início , Brasil , Estudos de Casos e Controles , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Doença de Parkinson/diagnóstico , Polimorfismo de Nucleotídeo ÚnicoAssuntos
Predisposição Genética para Doença/genética , Glucosilceramidase/genética , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Fatores Etários , Idoso , Brasil/epidemiologia , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Point mutations and genomic rearrangements in the MECP2 gene are the major cause of Rett syndrome (RTT), a pervasive developmental disorder affecting almost exclusively females. MECP2 mutations were also identified in patients with autism without RTT. In this study, we present a mutational and gene dosage analysis of the MECP2 in a cohort of 60 Brazilian males with autistic features but not RTT. No duplication or deletion was identified. Sequencing analysis, however, revealed four MECP2 sequence variations. Three of them were previously discussed as non disease causing mutations and one mutation (p.T160S) was novel. It affects a highly conserved amino acid located within the MBD domain, a region of the protein involved in specific recognition and interaction with methylated CpG dinucleotides. The p.T160S variation was not found in the control sample. This mutation may represent a potential genetic factor for autistic phenotype and should be object of further studies.
