Browsing by Issue Date, starting with "2018-03"
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- Next Generation Sequencing and Lysosomal Dysfunction: Novel mutations associated with Neurodegenerative disorders.Publication . Encarnação, Marisa; Coutinho, Maria Francisca; Matos, Liliana; Silva, Lisbeth; Ribeiro, Diogo; Nogueira, Célia; Vilarinho, Laura; Alves, SandraLysosomal Storage Disorders (LSD) are a group of inherited metabolic diseases characterized by a wide range in phenotypes and clinical variability. The diagnosis is often difficult and time consuming, with multiple tests/samples being required before a definitive diagnosis is reached. Next Generation Sequencing (NGS) is changing this scenario by allowing variant assessment at a large scale in a single run. The aim of this work was to develop an NGS-based workflow for the identification of LSD-causing variants. We designed a panel including exons and intronic flanking regions from 96 genes involved in lysosome homeostasis and function. The workflow was performed using a Sureselect protocol followed by sequencing in an Illumina MiSeq® platform. For alignment and variant anotation softwares Surecall and wANNOVAR were used. Validation of this custom-targeted panel was performed in 5 blind controls. For the studied cases, we could reach molecular diagnosis consistent with the clinical and biochemical diagnosis in 7 patients, corresponding to a diagnostic rate of 67% (7/11). For the undiagnosed patients, an extended custom panel composed also of autophagy modulators and other genes involved in lysosome biogenesis will be tested. From our first results we would like to highlight the detection of a novel frameshift mutation in the GM2A gene, which is associated with the extremely rare AB variant of Gangliosidosis, biochemically and clinically undistinguishable from the other two (Tay Sachs and Sandhoff Diseases). Also noteworthy, we were able to find out the molecular defect of a patient with a general clinical suspicion of Neuronal Ceroid Lipofuscinosis (CLN). From the 14 possible genes associated to these disorders, we detected the molecular defect in a single analysis. In fact, we identified a novel missense variant in the MFSD8 gene, reaching the diagnosis of a CLN7. Additionally, novel mutations in GLA, GALC, and NAGLU genes were found. We have also started a functional analysis to investigate the impact of two novel splicing mutations (GNPTAB and ARSB) and two novel missense mutations in NPC1 gene.
- Composition and bioaccessibility of elements in green seaweeds from fish pond aquaculturePublication . Afonso, C.; Cardoso, C,; Ripol, A.; Varela, J.; Quental-Ferreira, H.; Pousão-Ferreira, P.; Ventura, M.S.; Delgado, I.M.; Coelho, I.; Castanheira, I.; Bandarra, N.M.The elemental composition of five species of green seaweeds (Chaetomorpha linum, Rhizoclonium riparium, Ulva intestinalis, Ulva lactuca, Ulva prolifera) grown in fish pond aquaculture systems were studied. The elemental bioaccessibility in these species was also investigated through the application of an innovative in vitro digestive model of the human gastrointestinal tract. It was observed that R. riparium had the highest levels of Mn, Sr, Cd, Sn, and I and that U. lactuca had the highest Ni and Cu concentrations. The daily amounts of dried green seaweed required for achieving specific dietary intakes were calculated, namely: 7 g of dried U. lactuca (for meeting Cu Recommended Daily Allowance, RDA); 173 g of dried U. lactuca (Zn RDA); 78 g of dried C. linum (Se RDA); 41 g of dried C. linum (Mo RDA); and 0.5 g of dried R. riparium (I Dietary Reference Intake, DRI). Concerning elemental bioaccessibility, Mn and Cu had the highest values, always above 50%, I values were in the lower range, between 14 and 31%. The elemental bioaccessibility range of R. riparium (31–100%) was higher than the ranges for other species, particularly C. linum (0–56%). The bioaccessibility results entailed higher quantities of dried seaweed for reaching dietary intakes: 10 g of dried U. lactuca (Cu RDA); 290 g of dried R. riparium (Zn RDA); and 2 g of dried R. riparium (I DRI). Accordingly, R. riparium is a very rich I source. This study showed the importance of taking into account bioaccessibility results in estimating dietary intakes.
- Labial lesion in a Portuguese man returned from Brazil - The role of molecular diagnosisPublication . Ferreira, António; Silva, Augusta; Cruz, Mariana; Sabino, Raquel; Veríssimo, CristinaParacoccidioidomycosis is an acute - to chronic systemic mycosis caused by the fungus Paracoccidioides. Two species are recognized as causing paracoccidioidomycosis: Paracoccidioides brasiliensis and Paracoccidioides lutzii. Paracoccidioidomycosis is a commonly diagnosed fungal infection in South America and rare in Europe. Nevertheless, with the increase of immigration from endemic regions to European countries, clinicians must be aware of tropical infections and strongly consider them in differential diagnosis, having therefore the knowledge of all the available means necessary to identify specific pathogens. The authors present a case report of a Portuguese 46-year-old man who lived in Itaipava-Brazil for the past 21 years. In his return to Portugal, presented a lip lesion, weight loss, pulmonary infiltrates and cavities, and generalized adenopathies. An histopatologic diagnosis of mucocutaneous and pulmonary cryptococcosis was initially made. However, the negative result of cryptococcal antigen and the patient's epidemiology lead to the hypothesis of other etiological agent. All cultural examinations were negative, however the molecular detection of fungal DNA directly from tissue samples allowed the identification of the correct etiological agent as Paracoccidioides brasiliensis and the introduction of a most effective treatment for the management of this fungal infection. This was the first time that Paracoccidioides brasiliensis was identified by this PCR technique in Portugal.
- Relatório intercalar sobre a implementação da Estratégia Integrada para as Doenças Raras (2015-2020): Ano 2017Publication . Comissão Interministerial da Estratégia Integrada para as Doenças Raras (2015-2020)Conscientes da dimensão desta problemática em Portugal, estima-se que existam entre seiscentas a oitocentas mil pessoas portadoras destas doenças, foi constituída uma Comissão Interministerial para implementar a Estratégia Integrada para as Doenças Raras 2015-2020, baseada numa cooperação intersectorial e interinstitucional. Esta Estratégia Nacional é pioneira a nível europeu e surge em substituição do antigo Programa Nacional das Doenças Raras, o qual não conseguira responder às necessidades da pessoa com doença rara, por o seu âmbito de atuação extravasar o setor da Saúde. É objetivo desta Estratégia garantir que as pessoas com doenças raras tenham melhor acesso, qualidade dos cuidados de saúde e tratamento, com base nas evidências que a ciência tem vindo a produzir e maior celeridade e variedade de respostas sociais adaptadas a cada caso. Tem como missão desenvolver e melhorar: a) A coordenação dos cuidados; b) O acesso ao diagnóstico precoce; c) O acesso ao tratamento; d) A informação clínica e epidemiológica; e) A investigação; f) A inclusão social e a cidadania. A abordagem das doenças raras constitui, em si mesma, um desafio social e económico, assim, a Estratégia Integrada para as Doenças Raras 2015-2020 visa garantir que, de forma interministerial, intersectorial, interinstitucional e integrada, sejam reequacionadas as prioridades na abordagem global das doenças raras, reunindo os contributos, as competências e recursos de todos os sectores relevantes, de forma a estimular, ainda que de forma progressiva, uma mudança real nas condições complexas das pessoas que sofrem destas doenças, como previsto no Despacho n.º 2129-B/2015 de 27 de fevereiro. No âmbito das competências atribuídas a esta Comissão Interministerial apresenta-se o relatório anual sobre a implementação do plano anual 2017 da referida Estratégia.
- Como lidar com a Hipercolesterolemia Familiar (15-18 anos)Publication . HEART UK - The Cholesterol Charity; Instituto Nacional de Saúde Doutor Ricardo Jorge, IP (trad.)Trata-se da versão em língua portuguesa da autoria do Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis do INSA, do documento publicado originalmente em inglês pela HEART UK - The Cholesterol Charity. A publicação enquadra-se no âmbito do Estudo Português de Hipercolesterolemia Familiar, um estudo de investigação desenvolvido no INSA desde 1999. São objetivos deste projeto: i) Desenvolver estudos para conhecer melhor a realidade da Hipercolesterolemia Familiar em Portugal e no mundo; ii) Contribuir para um melhor diagnóstico e tratamento destes doentes realizando o teste genético; iii) Promover o treino dos profissionais que lidam com estes doentes. A coleção é constituída por três brochuras: A FH e eu; A minha família, a FH e eu; Como lidar com a FH.
- Risk-Benefit Assessment in foods: a case study involving mycotoxinsPublication . Alvito, Paula; Assunção, R.; Martins, Carla; Viegas, S.; Fernandes, P.; Carvalho-Oliveira, I.; Torres, D.; Lopes, C.; Monteiro, S.; Nabais, P.; Membré, J.M.; Boué, G.; Persson, M.; Thompsen, S.; Jakobsen, L.; Pires, S.; Poulsen, M.Over the last years, the contamination of different foodstuffs with multiple mycotoxins has been highly reported. Data from a recent Portuguese national project that studied the toxic effects of exposure of children under 3 years old to multiple mycotoxins in infant foods (MYCOMIX) reported the co-occurrence of twenty-one mycotoxins and metabolites present in breakfast cereals primarily marketed for children. This study showed that almost all of the analyzed breakfast cereal samples (96%) were contaminated with mycotoxins. The output of this project also highlighted the knowledge gaps on the contra-balance beneficial health effect of these foods, and the need to determine the risk-benefit balance, since the evaluated food products, namely breakfast cereals, are simultaneously recognized vehicles of food components, like nutrients, vitamins and water soluble and insoluble fibers, which could be assumed as beneficial for children health. Health risks associated with consumption of cereal-based foods, an important source of nutrients with beneficial health effects, could increase in the near future due to climate changes in Europe (dry conditions and increased ambient temperatures) thus the dissemination and use of the Risk-Benefit Assessment (RBA) harmonized tools in Europe would be of utmost importance to support food and health policies. Can we ever have a harmonized tool that enables food and health authorities to estimate the balance between risk and benefit of foods usually contaminated by mycotoxins, as cereals-based products? is a question that can be raised in an attempt to contribute to brainstorm under the topic of the 10th Conference of the World Mycotoxin Forum. “RiskBenefit4EU – Partnering to strengthen the risk-benefit assessment within EU using a holistic approach” (Grant Agreement Number GP/EFSA/AFSCO/2017/01 - GA02) is a recent European pilot project funded by EFSA and coordinated by Portugal (PT), integrating a multidisciplinary team from health and food institutes, national food safety authorities, R&D institutions and academia from PT, Denmark (DK) and France (FR). The main objectives of RiskBenefit4EU concerns the development of a set of RBA tools that can estimate the overall health effects of foods, food ingredients and diets and that can be applied to data from different countries. RiskBenefit4EU aims to strengthen the EU capacity to assess and integrate food risks and benefits in the areas of microbiological, nutritional and chemical components through the development of a harmonized framework. This pilot project will validate the RBA framework created using a Portuguese case study on breakfast cereals, including results obtained under MYCOMIX project.
- A minha família, a Hipercolesterolemia Familiar e eu (5-9 anos)Publication . HEART UK - The Cholesterol Charity; Instituto Nacional de Saúde Doutor Ricardo Jorge, IP (trad.)Trata-se da versão em língua portuguesa da autoria do Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis do INSA, do documento publicado originalmente em inglês pela HEART UK - The Cholesterol Charity. A publicação enquadra-se no âmbito do Estudo Português de Hipercolesterolemia Familiar, um estudo de investigação desenvolvido no INSA desde 1999. São objetivos deste projeto: i) Desenvolver estudos para conhecer melhor a realidade da Hipercolesterolemia Familiar em Portugal e no mundo; ii) Contribuir para um melhor diagnóstico e tratamento destes doentes realizando o teste genético; iii) Promover o treino dos profissionais que lidam com estes doentes. A coleção é constituída por três brochuras: A FH e eu; A minha família, a FH e eu; Como lidar com a FH.
- Editorial: Breakthroughs in top-down proteomicsPublication . Penque, Deborah; Marcus, Katrin; Torres, Vukosaca MilicIn this special issue, an updated overview on ‘where we are and where we are going in the area of top-down proteomics’ is given by Fornelli et al., one of the pioneering groups in top-down proteomics led by the proponent head of the term ‘proteoform’ and founder of the international Consortium in Top-Down Proteomics (CTDP), Neil Kelleher. Although being still technologically challenging, the rapid advances over the past years have demonstrated that the identification and characterization of thousands of proteoforms in high-throughput mode is today feasible for intact proteins< 30 kDa under denaturing condition. To further advance, the development of a new generation of instruments and softwares is still necessary, which may happen in the next coming years as predicted by the authors. The high molecular weight capability of native-top down proteomics, used today to characterize purified protein complexes under non-denaturing condition, is one of these technologies that could be innovated for high throughput top-down purposes. The main driver for this breakthrough is undoubtedly the wider acceptance and application of top-down approaches by proteomic researchers. This journey is already under way, as evidenced by the different articles presented in this special issue.
- Identification of OAF and PVRL1 as candidate genes for an ocular anomaly characterized by Peters anomaly type 2 and ectopia lentisPublication . David, Dezso; Anand, D.; Araújo, C.; Gloss, B.; Fino, J.; Dinger, M.; Lindahl, P.; Pöyhönen, M.; Hannele, L.; Lavinha, J.Keratolenticular dysgenesis (KLD) and ectopia lentis are congenital eye defects. The aim of this study is the identification of molecular genetic alterations responsible for those ocular anomalies with neurologic impairment in an individual with a de novo balanced chromosome translocation t(11;18)(q23.3;q11.2)dn. Disruption of OAF, the human orthologue of the Drosophila oaf, by the 11q23.3 breakpoint results in reduced expression of this transcriptional regulator. Furthermore, four most likely nonfunctional chimeric transcripts comprising up to OAF exon 3, derived from the der(11) allele, have also been identified. This locus has been implicated by publicly available genome-wide association data in corneal disease and corneal topography. The expression of the poliovírus receptor-related 1(PVRL1) or nectin cell adhesion molecule 1 (NECTIN1), a paralogue of nectin cell adhesion molecule 3 (PVRL3) associated with congenital ocular defects, situated 500 kb upstream from 11q23.3 breakpoint, is increased. The 18q11.2 breakpoint is localized between cutaneous T-cell lymphoma-associated antigen 1(CTAGE1) and retinoblastoma binding protein 8 (RBBP8) genes. Genomic imbalance that could contribute to the observed phenotype was excluded. Analysis of gene expression datasets throughout normal murine ocular lens embryogenesis suggests that OAF expression is significantly enriched in the lens from early stages of development through adulthood, whereas PVRL1 is lens-enriched until E12.5 and then down-regulated. This contrasts with the observation that the proposita's lymphoblastoid cell lines exhibit low OAF and high PVRL1 expression as compared to control, which offers further support that the alterations described above are most likely responsible for the clinical phenotype. Finally, gene interaction topology data for PVRL1 also agree with our proposal that disruption of OAF by the translocation breakpoint and misregulation of PVRL1 due to a position effect contribute to the observed ocular and neurological phenotype.
- Disponibilidade e necessidades de informação no domínio dos contaminantes químicos em alimentos: relatórioPublication . Brazão, Roberto; Inácio, Patrícia; PortFIR – Grupo de Trabalho Gestão de Informação (GTGI)Apresentação dos resultados do inquérito realizado para avaliar a disponibilidade e necessidades de informação no domínio dos contaminantes químicos em alimentos, junto dos principais stakeholders de diversos setores: alimentar, da saúde, do ensino e investigação, da administração pública, entre outros (não inclui os Organismos de Estado).