Browsing by Author "Oliveira, Alexandra"
Now showing 1 - 5 of 5
Results Per Page
Sort Options
- Evidence for an association of prenatal exposure to particulate matter with clinical severity of Autism Spectrum DisorderPublication . Santos, João Xavier; Sampaio, Pedro; Rasga, Célia; Martiniano, Hugo; Faria, Clarissa; Café, Cátia; Oliveira, Alexandra; Duque, Frederico; Oliveira, Guiomar; Sousa, Lisete; Nunes, Ana; Moura Vicente, AstridEarly-life exposure to air pollutants, including ozone (O3), particulate matter (PM2.5 or PM10, depending on diameter of particles), nitrogen dioxide (NO2) and sulfur dioxide (SO2) has been suggested to contribute to the etiology of Autism Spectrum Disorder (ASD). In this study, we used air quality monitoring data to examine whether mothers of children with ASD were exposed to high levels of air pollutants during critical periods of pregnancy, and if higher exposure levels may lead to a higher clinical severity in their offspring. We used public data from the Portuguese Environment Agency to estimate exposure to these pollutants during the first, second and third trimesters of pregnancy, full pregnancy and first year of life of the child, for 217 subjects with ASD born between 2003 and 2016. These subjects were stratified in two subgroups according to clinical severity, as defined by the Autism Diagnostic Observational Schedule (ADOS). For all time periods, the average levels of PM2.5, PM10 and NO2 to which the subjects were exposed were within the admissible levels defined by the European Union. However, a fraction of these subjects showed exposure to levels of PM2.5 and PM10 above the admissible threshold. A higher clinical severity was associated with higher exposure to PM2.5 (p = 0.001), NO2 (p = 0.011) and PM10 (p = 0.041) during the first trimester of pregnancy, when compared with milder clinical severity. After logistic regression, associations with higher clinical severity were identified for PM2.5 exposure during the first trimester (p = 0.002; OR = 1.14, 95%CI: 1.05–1.23) and full pregnancy (p = 0.04; OR = 1.07, 95%CI: 1.00–1.15) and for PM10 (p = 0.02; OR = 1.07, 95%CI: 1.01–1.14) exposure during the third trimester. Exposure to PM is known to elicit neuropathological mechanisms associated with ASD, including neuroinflammation, mitochondrial disruptions, oxidative stress and epigenetic changes. These results offer new insights on the impact of earlylife exposure to PM in ASD clinical severity.
- Prevalence of Autism Spectrum Disorder in the Centro region of Portugal: a population based study of school age children within the ASDEU projectPublication . Rasga, Célia; Santos, João Xavier; Café, Cátia; Oliveira, Alexandra; Duque, Frederico; Posada, Manuel; Nunes, Ana; Oliveira, Guiomar; Vicente, Astrid MouraIntroduction: Accurate prevalence estimates for Autism Spectrum Disorder (ASD) are fundamental to adequately program medical and educational resources for children. However, estimates vary globally and across Europe, and it is therefore wise to conduct epidemiological studies in defined geo-cultural contexts. Methods: We used a population screening approach to estimate the prevalence of ASD in the Centro region of Portugal, using a harmonized protocol as part of the Autism Spectrum Disorders in the European Union (ASDEU) project. Results: The overall prevalence was estimated at 0.5% (95% CI 0.3-0.7), higher in schools with Autism Units (3.3%, 95%CI 2.7-3.9) than in regular schools (0.3%, 95% CI 0.1-0.5) or schools with Multiple Disability Units (0.3%, 95% CI 0.04-0.6). Discussion: The results indicate that the diagnosis of ASD is followed by the most effective educational policies in Centro Region. The variability in prevalence estimates across the different regions from the ASDEU project, and globally, is discussed.
- Prevalência da perturbação do espectro do autismo na região Centro de Portugal: um estudo no âmbito do projeto ASDEUPublication . Rasga, Célia; Santos, João Xavier; Café, Cátia; Oliveira, Alexandra; Duque, Frederico; Nunes, Ana; Oliveira, Guiomar; Vicente, Astrid MouraA prevalência da perturbação do espectro do autismo (PEA) em crianças foi estimada na região Centro de Portugal, no âmbito do projeto Autism Spectrum Disorders in the European Union (ASDEU). A metodologia de estudo baseou-se no rastreio de crianças entre os 7 e 9 anos matriculadas, no ano letivo de 2016/2017, em escolas primárias desta região. O rastreio incluiu todas as escolas com unidades de apoio especializado para crianças com problemas de neurodesenvolvimento e cerca de 10% das escolas regulares, selecionadas aleatoriamente. A sinalização das crianças foi feita pelos professores com recurso a um questionário estruturado, previamente validado, após consentimento parental. O diagnóstico foi feito através de avaliação clínica e funcional direta por equipa clínica especializada. Foram rastreadas 13 690 crianças de 173 escolas. A prevalência estimada para a PEA na região Centro foi de 0,5% (IC95% 0,3-0,7). Nas escolas com unidades de apoio especializado para autismo, observou-se uma prevalência substancialmente mais elevada de 3,3% (IC95% 2,7-3,9), indicando que a maioria das crianças está a receber o apoio educativo mais indicado. A prevalência de PEA na região Centro foi comparável a outros países envolvidos no projeto ASDEU, tendo-se, no entanto, observado assimetrias regionais na Europa.
- Prevalência da perturbação do espectro do autismo na região Centro de Portugal: Um estudo no âmbito do projeto ASDEUPublication . Rasga, Célia; Santos, João; Café, Cátia; Oliveira, Alexandra; Duque, Frederico; Nunes, Ana; Oliveira, Guiomar; Vicente, AstridA prevalência da perturbação do espectro do autismo (PEA) em crianças foi estimada na região Centro de Portugal, no âmbito do projeto Autism Spectrum Disorders in the European Union (ASDEU). A metodologia de estudo baseou-se no rastreio de crianças entre os 7 e 9 anos matricula- das, no ano letivo de 2016/2017, em escolas primárias desta região. O rastreio incluiu todas as escolas com unidades de apoio especializado para crianças com problemas de neurodesenvolvimento e cerca de 10% das escolas regulares, selecionadas aleatoriamente. A sinalização das crianças foi feita pelos professores com recurso a um questionário estruturado, previamente validado, após consentimento parental. O diagnóstico foi feito através de avaliação clínica e funcional direta por equipa clínica especializada. Foram rastreadas 13 690 crianças de 173 escolas. A prevalência estimada para a PEA na região Centro foi de 0,5% (IC95% 0,3-0,7). Nas escolas com unidades de apoio especializado para autismo, observou-se uma prevalência substancialmente mais elevada de 3,3% (IC95% 2,7-3,9), indicando que a maioria das crianças está a receber o apoio educativo mais indicado. A prevalência de PEA na região Centro foi comparável a outros países envolvidos no projeto ASDEU, tendo-se, no entanto, observado assimetrias regionais na Europa.
- Widening the Spectrum of TMPRSS6 Gene Pathogenic Variants Related with Hereditary Iron DeficiencyPublication . Pessoa, Vera; Oliveira, Alexandra; Santos, Daniela; Mendonça, Joana; Machado, Miguel P.; Ferrão, José; Vieira, Luís; Lopes, Pedro; Kislaya, Irina; Matias-Dias, Carlos; Barreto, Marta; Faustino, PaulaIron-Refractory Iron-Deficiency Anemia (IRIDA) is a rare autosomal recessive hypochromic microcytic anemia derived from loss-of-function mutations in the TMPRSS6 gene, which encodes Matriptase-2, a negative regulator of hepcidin expression. IRIDA patients have high hepcidin levels that prevent iron absorption and recycling. Very few studies concerning this pathology have been carried out in the Portuguese population and its molecular basis is still largely unknown. In this study, we aimed to identify genetic variants in TMPRSS6 in a sample of the Portuguese population with a hematological phenotype suggestive of iron deficiency. In addition, we intended to evaluate the performance of NGS for genetic screening of this large gene. We studied 100 adults with anemia and/or microcytosis and/or hypochromia collected by the Portuguese National Health Examination Survey (INSEF). Other possible genetic causes for these abnormal phenotypes, namely α- and β-thalassemia, were discarded after HBA1, HBA2 and HBB genetic screening. The TMPRSS6 gene (18 coding regions, exon/intron boundaries and regulatory regions) was amplified in 3 long-PCR fragments that were screened by NGS using Nextera XT libraries in a MiSeq platform. The genetic variants found were validated by Sanger sequencing (transcript ENST00000676104.1). Several known variants were identified along with two unreported mutations, c.1585T>C (p.Cys529Arg) and c.1580T>G (p.Phe527Cys). These novel mutations were classified as pathogenic by in silico analyses through Polyphen2, SIFT, and Missense3D. Moreover, Phyre2 software was used to produce a 3D structure of the mutated proteins, based on alignments with known protein structures, as there is no 3D model for Matriptase-2 on online databases. The two novel mutations were found in heterozygosity, explaining the mild abnormal hematological phenotypes and serum iron biomarkers presented by both patients. Functional studies should be performed to validate these findings. Our results widened the spectrum of TMPRSS6 pathogenic variants underlying hereditary iron deficiency-related pathologies. In addition, NGS revealed to be an appropriate tool for TMPRSS6 genetic screening.