RESUMO
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.
Assuntos
Transtorno Autístico/genética , Proteína 2 de Ligação a Metil-CpG/genética , Mutação de Sentido Incorreto/genética , Brasil , Criança , Ilhas de CpG/genética , Análise Mutacional de DNA , Humanos , Masculino , Proteína 2 de Ligação a Metil-CpG/químicaRESUMO
In the last decade, several genes have been linked to Parkinson's disease (PD), including GIGYF2, ATP13A2 and GBA. To explore whether mutations in these genes contribute to development of PD in the Brazilian population, we screened 110 patients with early-onset PD. No clearly pathogenic mutations were identified in ATP13A2 and GIGYF2. In contrast, we identified a significantly higher frequency of known pathogenic mutations in GBA gene among the PD cases (6/110=5.4%) when compared to the control group (0/155) (P=0.0047). Our results strongly support an association between GBA gene mutations and an increased risk of PD. Mutations in GIGYF2 and ATP13A2 do not seem to represent a risk factor to the development of PD in the Brazilian population. Considering the scarcity of studies on GIGYF2, ATP13A2 and GBA mutation frequency in Latin American countries, we present significant data about the contribution of these genes to PD susceptibility.
