DGH - Posters/abstracts em congressos internacionais
URI permanente para esta coleção:
Navegar
Percorrer DGH - Posters/abstracts em congressos internacionais por Domínios Científicos e Tecnológicos (FOS) "Ciências Médicas::Ciências da Saúde"
A mostrar 1 - 7 de 7
Resultados por página
Opções de ordenação
- Analysis and evaluation of genotoxicity and carcinogenicity assessment in EU legislation to improve regulatory implementation of NAMs: A focus on in silico approachesPublication . Bossa, Cecília; Raitano, Giuseppa; Benfenati, Emilio; Alivernini, Silvia; Andreoli, Cristina; Aquilina, G.; Attias, L.; Dusinska, Maria; El Yamani, N.; Louro, Henriqueta; Marcon, Francesca; Rundèn-Pran, E.; Russo, Maria Teresa; Silva, Maria João; Battistelli, Chiara LauraGenotoxicity and carcinogenicity are key endpoints for the risk assessment of all types of substances. Research on alternatives to animal testing for these endpoints has been active for decades, leading to the development of short-term in vitro tests that are integrated into current testing strategies. Nevertheless, high relevance is still devoted to data from in vivo studies. In parallel, progress in the comprehension of mechanisms underpinning genotoxicity and genotoxic carcinogenicity processes, together with the analysis of the great wealth of experimental data produced, allowed the discovery of structural determinants utilized in quantitative and qualitative structure-activity relationships and enabling in silico predictions of these endpoints. Presented here is a case study part of the collective effort carried out within the European Partnership for the Assessment of Risks from Chemicals (PARC) to address the challenges associated with innovation in chemical risk assessment, including the phasing out of animal testing through the introduction of New Approach Methodologies (NAMs) [1,2]. The case study aims to analyze current practices of the regulatory evaluation of genotoxicity and carcinogenicity hazard in several EU frameworks, in order to highlight needs and challenges in the actual or potential use of NAMs as well as short-and long- term goals towards the overcoming of animal testing. Among other NAMs, we are focusing on the role of in silico approaches highlighting strategies to increase the regulatory application and acceptance of QSAR based approaches. To this aim, the OECD QSAR Assessment Framework [3,4] has been identified as a suitable tool for evaluating the models and their predictions and will be applied to selected case studies. Moreover, a list of human relevant carcinogens has been developed as reference chemicals to evaluate and possibly refine in silico methodologies supporting a human-centric paradigm shift in toxicology.
- Dysregulated gene expression in colorectal cancer upon exposure to bisphenol A alternatives - a new approachPublication . Lacerda, Rafaela; Ventura, Célia; Louro, Henriqueta; Silva, Maria João; Romão, LuísaBisphenol A (BPA) has been widely used in plastics and resins since the 1950s, making it a common part of everyday products like food containers and bottle linings. Alternative substances are increasingly replacing BPA, but they are raising health and environmental concerns. Some mimic BPA’s endocrine-disrupting effects, while others affect different biological pathways. Substitutions in bisphenols can alter their biological properties, including nuclear receptor activation. Some BPA alternatives, like BPS, BPF and BPZ, may also pose cancer risks by activating oestrogen receptors, potentially even more than BPA itself. They may also contribute to colorectal cancer (CRC). Research suggests that BPA and its substitutes can influence cancer progression by altering cellular pathways, promoting metastasis and affecting gene expression. One of the key steps in gene expression regulation is translation initiation, whose canonical pathway is globally impaired under stress conditions, like exposure to BPA alternatives. Thus, we will subject NCM460 (normal intestinal mucosa) and HCT116 (colorectal carcinoma) cells to BPS, BPF and BPZ exposure and identify the transcripts actively being translated in such conditions, using ribosome profiling. We will analyse data with the R package anota2seq and evaluate the positively identified targets (compared to total RNA sequencing) for the existence of alternative mechanisms of translation initiation regulating their expression. The accurate characterisation of such mechanisms will be crucial for designing antisense RNA oligomers (ASOs) for potential therapeutic approaches. We will evaluate the cytotoxic effects of BPS, BPF and BPZ in the presence or absence of the selected alternatively translated transcripts (functional or targeted with the designed ASOs). Cytotoxic effects will be assessed through in vitro assays, analysing metabolic activity, membrane integrity, and cell proliferation. Thus, our research explores protein synthesis dysregulation to reduce CRC risks from BPS, BPF and BPZ exposure — an emerging public health issue.
- Forty-four years of newborn screening in Portugal: new challenges, the same commitment to the communityPublication . Marcão, Ana; Sousa, Carmen; Pinho, Conceição; Ribeiro, Diogo; Rodrigues, Diogo; Guimarães, Fábio; Fonseca, Helena; Rocha, Hugo; Carvalho, Ivone; Lopes, Lurdes; Vilarinho, LauraIntrodução: O Programa Nacional de Rastreio Neonatal (PNRN) é um programa sistemático destinado a todos os recém-nascidos (RN) com nascimento em Portugal, e que atualmente inclui 28 patologias, das quais uma em estudo piloto. O aumento do número de patologias rastreadas, a implementação de novas e mais complexas técnicas de rastreio, o aumento da diversidade genética da população Portuguesa, os novos hábitos dietéticos e a exigência crescente da sociedade atual, trouxeram desafios que exigiram uma adaptação permanente do programa ao longo destes anos. Material e métodos: Mais de 4, 200 000 RN foram rastreados desde 1979. Diferentes métodos e estratégias de rastreio foram utilizados ao longo destes 44 anos. Atualmente, utilizam-se técnicas imunológicas (HC e CF), espectrometria de massa em tandem (IEM), eletroforese capilar (SCD) e estudo genético (FQ e SMA). Resultados: A antecipação da data de colheita (3º-6º dia), e a publicação de resultados na internet foram importantes mudanças organizacionais do programa. A alteração do protocolo de colheitas nos RN grandes prematuros veio responder à necessidade de evitar resultados falsos negativos no rastreio do CH. A performance do rastreio das 24 IEM foi claramente melhorada com a introdução de vários testes de segunda linha na estratégia de rastreio. A alteração recente da estratégia de rastreio da CF (2023), passando a incluir o estudo genético, trouxe uma melhoria extraordinária na performance deste rastreio, esperando-se ainda uma melhoria acrescida com uma nova alteração introduzida em 2024. As alterações efetuadas permitiram aumentar a sensibilidade e especificidade de deteção das várias patologias rastreadas e melhorar a resposta do PNRN à comunidade. Conclusão: O PNRN é um programa dinâmico que se mantém em constante atualização, quer em termos organizacionais e comunicacionais, quer em termos de patologias rastreadas e estratégias de rastreio. Desde 1979, mais de 2,700 casos positivos foram identificados e referenciados para CR, permitindo uma intervenção terapêutica adequada, com benefício dos RN e das famílias. A atualização permanente dos programas de rastreio, com adaptação constante aos novos desafios tecnológicos e às mudanças emergentes na comunidade a que se dirigem é fundamental para o seu sucesso.
- Genetic Analysis of Early and Recurrent Pregnancy Loss: Challenges and AdvancesPublication . Ferreira, Cristina; Tarelho, Ana Rita; Pedro, Sónia; Marques, Bárbara; Viegas, Mónica; Correia, HildebertoPregnancy loss is defined as the spontaneous termination of a pregnancy before fetal viability and affects approximately one in four pregnancies. Genetic analysis of early or recurrent fetal losses is crucial for elucidating the underlying causes of miscarriage, thereby guiding clinical management and providing prognostic information to affected couples. Genetic anomalies, particularly chromosomal abnormalities, are implicated in approximately 50% to 70% of spontaneous abortions in the first trimester. Identifying these anomalies aids in understanding the etiology of pregnancy loss and offers valuable insights for future reproductive planning. Various sample types and genetic testing methodologies are employed in this context, each with distinct advantages and limitations. Traditional cytogenetic analysis, such as karyotyping, requires viable fetal cells obtained through culture. However, this method has a success rate of only about 58% due to potential culture failures and maternal cell contamination, which can lead to inconclusive or misleading results. In contrast, molecular techniques like chromosomal microarray analysis (CMA) do not rely on cell culture, offering higher resolution in detecting chromosomal abnormalities, improving diagnostic yield, and reducing the incidence of inconclusive results. However, CMA requires a sufficient amount of fetal DNA, which may be difficult to obtain due to maternal contamination or the challenge of collecting the conceptus product. The use of cell-free fetal DNA (cffDNA) from maternal blood has emerged as a promising method for evaluating fetal ploidy status, although large-scale validation of this approach is still required. In this study, we present our laboratory's experience in analyzing different sample types and employing various methodologies to investigate pregnancy loss. Our findings contribute to the ongoing discussion on optimizing genetic diagnostic strategies for early and recurrent pregnancy loss, improving patient outcomes, and informing future research directions.
- Multiple non-contiguous interstitial deletions in 5q21q22.1, including the CHD1 gene, identified in a boy with developmental delay and severe language impairmentPublication . Marques, Bárbara; Pedro, Sónia; Serafim, Sílvia; Tarelho, Ana Rita; Ferreira, Cristina; Catanho, Joana Adelaide; Moreira, Ana; Carvalho, Inês; Correia, HildebertoIntellectual disability (ID), developmental delay (DD), and behavioural disorders are complex neurodevelopmental conditions associated with multifactorial etiologies, including genetic factors. Chromosomal microarray analysis (CMA) is a valuable tool in identifying copy number variations (CNVs) contributing to neurodevelopmental disorders. Here we report a 4-year-old male with DD, severe language impairment, behavioral disturbances, macrocephaly, facial dysmorphisms, and delay walking (at 20 months). He was born to nonconsanguineous parents. Family history is significant for maternal intellectual disability and paternal neonatal hypoxic-ischemic encephalopathy, which resulted in hemiparesis and language impairment. CMA revealed three heterozygous interstitial deletions: 2.12Mb at 5q15q21.1(97929163-100045362), encompassing the CHD1 gene; 684Kb at 5q21.3(104580978-105264711), a gene-free region; and 3.69Mb at 5q21.3q22.1(107047547-110727429), including the SLC25A46 gene. Parental segregation studies revealed that all three deletions were maternally inherited. Although the identified non-contiguous losses may suggest a complex chromosomal rearrangement (CCR), no further studies were performed. Interstitial deletions of the middle region of the long arm of chromosome 5 are rare, and cases of CCR involving only this chromosome are even more rare. Most of the CCR are associated to intellectual disability. Missense variants in CHD1 have been associated with Pilarowski-Bjornsson syndrome, a neurodevelopmental disorder characterized by ID, DD, dysmorphic features, and apraxia of speech. However, deletion involving this gene are rare and may lead to speech abnormalities in the absence of intellectual disability (ID) or other major neurodevelopmental disorders. This phenotypic variability suggests that both CHD1 deletions and missense variants may exhibit variable expressivity or incomplete penetrance. This case highlights a possible link between CHD1 deletion and an autosomal dominant complex neurodevelopmental disorder and the diagnostic utility of cytogenetic studies in identifying complex genetic etiologies underlying CCR.
- Reverse phenotyping after ngs panel of x-linked intellectual disability unravels creatine transporter (SLC6A8) deficiencyPublication . Padeira, Gonçalo; Jacinto, Sandra; Venâncio, Margarida; Marcão, Ana; Conceição, Carla; Ferreira, Ana CristinaX-linked intellectual disability (XLID) is characterized by extensive genetic heterogeneity. Next-generation sequencing (NGS) have been used in these cases as a cost-effective diagnosis approach. Genetic findings often reveal variants unforeseen during clinical investigation, prompting the need for reevaluation of specific features designated as reverse phenotyping (RP). X-linked creatine transporter deficiency (CTD) is a potentially treatable intellectual disability caused by pathogenic variants in the SLC6A8 gene leading to impaired creatine transport into the brain. A 7-year-old boy with intellectual disability, speech delay, hyperactivity and epilepsy was referred to Metabolic and Neuropediatric Clinic. Family history identified a mother with learning difficulties and a maternal uncle with intellectual disability, indicating a possible X-linked inheritance. NGS intellectual disability panel identified a variant classified as probably pathogenic (c.880_881del (p(Lys294Alafs*2)) in the SLC6A8 gene, in hemizygosity which prompted referral to Metabolic and Neuropediatric Clinic. Reverse phenotyping was carried out with biochemical and imaging assessment that showed: high urinary Creatine-Creatinine ratio (2.17; RV 0.04-1.07) with normal guanidinoacetate acid and absence of creatine peak in brain MRI spectroscopy, confirming the diagnosis. Genetic studies on female family members are ongoing. He started treatment with creatine, arginine and glycine in the last appointment. CTD is a rare disease that has been reported in more than 150 individuals worldwide. We present a case in which the diagnostic approach was reverse phenotyping, through biochemical and imaging studies, after the identification of pathogenic variants in SLC6A8 by NGS panel. The efficacy of its treatment remains controversial with variable results, and a close evaluation will be needed.
- Twenty Years of Newborn Screening for MCADD in Portugal: genetic dataPublication . Fonseca, Helena; Marcão, Ana; Sousa, Carmen; Rocha, Hugo; Vilarinho, LauraIntroduction: Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is an autosomal recessive inherited metabolic disorder that affects fatty acid oxidation metabolism. Most cases present the most common c.985G>A mutation in ACADM gene, while a few patients carry other rare mutations. In Portugal, MCADD has been included in the newborn screening program since 2004 and is the most frequently diagnosed inborn error of metabolism detected through this program, with an incidence of 1 in 6,433. Materials and Methods: Approximately 1,762,713 newborns were screened for MCAD deficiency between October 2004 and January 2025, using tandem mass spectrometry (MS/MS) to detect elevated octanoylcarnitine (C8) levels and an increased C8/C10 ratio. Tandem mass spectrometry (MS/MS) results and genetic testing data were analyzed. Results: Over the 20 years period, a total of 274 newborns were identified with high values of C8 and C8/C10 ratios from dried blood spots. Biochemical and molecular follow up confirmed the MCADD diagnosis in 273 cases. Molecular characterization was not available for 90 cases. Of the remaining 183 cases, which were studied at our Newborn Screening, Metabolism and Genetics Unit, 162 (88%) were homozygous for the c.985G>A mutation, while 22 were compound heterozygotes. Of these, 13 carried the c.985G>A mutation along with a another mutation, whereas 8 had two distinct mutations. Additionally, seven novel mutations were identified in this cohort: c.94G>C, c.113G>C, c.214G>T, c.532A>T, c.974A>G, c.1133G>A, and c.708+1G>A. Conclusion: Newborn screening has been crucial for identifying and managing of MCADD in Portugal. Our study confirms the c.985G>A mutation as the most frequent pathogenic variant, consistent with previous reports. The identification of seven novel mutations expands the spectrum of known variants, underscoring the importance of comprehensive genetic analysis. These findings reinforce the importance of newborn screening in early diagnosis and intervention, while also contributing to a deeper understanding of the genetic diversity of MCADD, with implications for genetic counseling and long-term management.