Browsing by Author "Alves, Ana C."
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- Cardiopatia complexa num feto com deleção terminal em 6q27Publication . Laurentino, Simão R.; Serafim, Sílvia S.; Marques, Bárbara S.; Pedro, Sónia I.; Ferreira, Cristina M.; Tarelho, Ana R.; Brito, Filomena T.; Silva, Marisa D.; Alves, Ana C.; Peliano, Ricardo C.; Viegas, Mónica I.; Carrilho, Bruno M.; Carvalho, Inês S.; Teixeira, Ana M.; Martins, Ana T.; Cohen, Álvaro E.; Correia, Hildeberto O.Caso de uma grávida com 38 anos, referenciada por ecocardiograma precoce (15 semanas) sugestivo de cardiopatia complexa parecendo tratar-se de truncus arteriosus com arco truncal direito. O teste genético de rastreio pré-natal não invasivo (NIPS) para as aneuploidias mais comuns havia dado um resultado considerado de baixo risco. Fez-se colheita de vilosidades coriónicas (BVC). O estudo por microarray é o teste genético recomendado nas gestações com anomalias ecográficas. Assim, pretende-se estabelecer uma relação causal entre as anomalias observadas no feto e uma alteração genética.
- Estudo Português de Hipercolesterolemia Familiar: 1999-2020Publication . Medeiros, Ana M.; Alves, Ana C.; Chora, Joana R.; Bourbon, MafaldaA Hipercolesterolemia Familiar (FH) é uma doença genética do metabolismo dos lípidos, para a qual existem métodos de diagnóstico e tratamentos eficazes disponíveis. Em Portugal estima-se que existam entre 20 000–33 000 pessoas com FH (prevalência 1:500–1:300). Indivíduos com FH possuem um elevado risco de desenvolver uma doença cardiovascular prematura (DCV), pois apresentam valores de colesterol elevados desde a nascença. O diagnóstico genético inclui o estudo de 3 genes associados à FH: LDLR, APOB, PCSK93. O Estudo Português de Hipercolesterolemia Familiar teve início em 1999 e tem como objetivo identificar a causa da genética da hipercolerolemia em indivíduos com critérios clínicos de FH.
- Functional Analysis of LDLR (Low-Density Lipoprotein Receptor) Variants in Patient Lymphocytes to Assess the Effect of Evinacumab in Homozygous Familial Hypercholesterolemia Patients With a Spectrum of LDLR ActivityPublication . Banerjee, Poulabi; Chan, Kuo-Chen; Tarabocchia, Michel; Benito-Vicente, Asier; Alves, Ana C.; Uribe, Kepa B.; Bourbon, Mafalda; Skiba, Paul J.; Pordy, Robert; Gipe, Daniel A.; Gaudet, Daniel; Martin, CesarOBJECTIVE: Homozygous familial hypercholesterolemia is a rare disease usually caused by LDLR (low-density lipoprotein receptor) mutations. Homozygous familial hypercholesterolemia is characterized by markedly elevated LDL-C (low-density lipoprotein cholesterol) levels and an extremely high risk of premature atherosclerotic cardiovascular disease. A phase 2, proof-of-concept study (NCT02265952) demonstrated that evinacumab, a fully human monoclonal antibody to ANGPTL3 (angiopoietin-like 3 protein), reduced LDL-C levels in 9 patients with genotypically confirmed homozygous familial hypercholesterolemia and was well tolerated. The aim of this study was to analyze the effects of evinacumab on LDLR activity in lymphocytes purified from patients in the proof-of-concept study. APPROACH AND RESULTS: LDLR activity was assessed in patient lymphocytes before and after treatment with evinacumab and versus lymphocytes carrying wild-type LDLR, and also in an LDLR-defective Chinese hamster ovary cell line (CHO-ldlA7) transfected with plasmids encoding the LDLR variants. Overall mean peak reduction in LDL-C with evinacumab was −58±18%, occurring between Week 4 and Week 12. Mutations identified in the 9 patients were shown to be pathogenic, with loss of LDLR activity versus wild type. Two of the LDLR variants, p.(Cys681*) and p.(Ala627Profs*38), were class 2 type mutations that are retained in the endoplasmic reticulum. Six variants were class 3 type mutations with impaired LDL-C binding activity: p.(Trp87Gly), occurring in 2 patients, p.(Gln254Pro), p.(Ser177Leu), p.(Gly335Val), and p.(Ser306Leu). Evinacumab had no effect on LDLR activity. CONCLUSIONS: These results suggest that evinacumab is effective for lowering LDL-C in patients with homozygous familial hypercholesterolemia, and the inhibition of ANGPTL3 in humans lowers LDL-C in a mechanism independent of the LDLR.
- Genomics of familial hypercholesterolaemiaPublication . Alves, Ana C.; Chora, Joana R.; Bourbon, MafaldaFamilial hypercholesterolaemia is an autosomal dominant disorder of lipid metabolism characterized by elevated levels of LDL-C and increased cardiovascular risk. Although the disorder can be diagnosed based on established clinical criteria, only the genetic diagnosis confirms the clinical suspicion. There are three main genes associated with familial hypercholesterolaemia: LDL receptor (LDLR), responsible for more than 90% of the cases, apolipoprotein B (APOB), responsible for 5–10% of the cases and Proprotein Convertase Subtilisin/ Kexin Type 9 (PCSK9), responsible for up to 3% of the cases. However, reporting of situations where there is an overlap of the familial hypercholesterolaemia phenotype and other conditions is now growing. (...)
- Improving Familial Hypercholesterolaemia Diagnosis – Functional in Vitro Analysis of LDLR Missense Variants Found in the Portuguese FH CohortPublication . Alves, Ana C.; Graça, Rafael; Bourbon, MafaldaObjective: Familial Hypercholesterolaemia (FH) is an autosomal disorder of lipid metabolism presenting with increased cardiovascular risk due to lifelong exposure to high LDL values. LDLR mutations are the cause of disease in 90% of the cases but proof of pathogenicity has only been obtained for about 10%. The lack of functional characterization of variants found in patients with a clinical diagnosis of FH makes it difficult to reach a definite FH diagnosis.
- Single versus Multiple Imputation Methods Applied to Classify Dyslipidemic Patients Concerning Statin Usage: a Comparative Performance StudyPublication . Albuquerque, João; Alves, Ana C.; Medeiros, Ana M.; Bourbon, Mafalda; Antunes, MaríliaIntroduction: One ofthe greatest challenges when working with clinical datasetsisto decide howto deal withmissing values. Removing observations with any missing values priorto data analysis, a process defined aslistwise deletion, is the standard default procedure in most statistical software packages, but may lead to great loss of valuable information [1]. The use of robust imputation methods may provide accurate estimates for missing values, allowing to include these observations into the analysis. The imputation strategy to adopt depends on the amount and type of missing information, and also on the relation between variables, allying statistical expertise with clinical understanding of the data. The main purpose of this work was to compare the performance oftwo differentmethods ofimputationto overcomemissingness on dyslipidemic patients regarding statin usage.