Browsing by Author "Medeiros, A.M."
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- Analysis of publicly available LDLR, APOB, and PCSK9 variants associated with familial hypercholesterolemia: application of ACMG guidelines and implications for familial hypercholesterolemia diagnosisPublication . Chora, J.R.; Medeiros, A.M.; Alves, A.C.; Bourbon, M.PurposeFamilial hypercholesterolemia (FH) is an autosomal disorder of lipid metabolism presenting with increased cardiovascular risk. Although more than 1,700 variants have been associated with FH, the great majority have not been functionally proved to affect the low-density lipoprotein receptor cycle. We aimed to classify all described variants associated with FH and to establish the proportion of variants that lack evidence to support their pathogenicity.MethodsWe followed American College of Medical Genetics and Genomics (ACMG) guidelines for the classification, and collected information from a variety of databases and individual reports. A worldwide overview of publicly available FH variants was also performed.ResultsA total of 2,104 unique variants were identified as being associated with FH, but only 166 variants have been proven by complete in vitro functional studies to be causative of disease. Additionally, applying the ACMG guidelines, 1,097 variants were considered pathogenic or likely pathogenic. Only seven variants were found in all five continents.ConclusionThe lack of functional evidence for about 85% of all variants found in FH patients can compromise FH diagnosis and patient prognosis. ACMG classification improves variant interpretation, but functional studies are necessary to understand the effect of about 40% of all variants reported. Nevertheless, ACMG guidelines need to be adapted to FH for a better diagnosis.
- Analysis of publicly available LDLR, APOB, and PCSK9 variants associated with familial hypercholesterolemia: application of ACMG guidelines and implications for familial hypercholesterolemia diagnosisPublication . Chora, J.R.; Medeiros, A.M.; Alves, A.C.; Bourbon, M.Familial Hypercholesterolemia (FH): Lipid metabolism autosomal dominant condition; Patients present elevated low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) values since birth - elevated cardiovascular risk.
- ApoB/ApoA1 ratio improves clinical criteria sensitivity for the identification of FH childrenPublication . Medeiros, A.M.; Alves, A.C.; Aguiar, P.; Bourbon, M.
- Caracterização bioquímica e molecular de doentes com hipercolesterolemias genéticasPublication . Alves, A.C.; Medeiros, A.M.; Gomes, A.; Bourbon, M.O colesterol elevado no sangue contribui para o processo arterosclerótico, que está na base das doenças cardiovasculares (DCV). Perturbações no metabolismo lipídico podem dever-se a alterações nos receptores ou seus ligandos, como é o caso da Hipercolesterolemia Familiar (FH). A FH é uma doença autossómica dominante que se caracteriza a nível clínico por níveis elevados de cLDL, levando ao aparecimento prematuro de doenças cardiovasculares. A nível genético esta doença caracteriza-se por mutações em três genes: LDLR, APOB e PCSK9. O objectivo deste estudo foi analisar o perfil bioquímico e molecular de doentes com FH diagnosticada clinicamente e o aparecimento de doença cardiovascular prematura nos doentes referenciados ao Estudo Português de Hipercolesterolemia Familiar (EPFH).
- Cardiovascular risk assessment of dyslipidemic children: analysis of biomarkers for the correct assessment of monogenic dyslipidemiaPublication . Medeiros, A.M.; Alves, A.C.; Aguiar, P.; Bourbon, M.; Estudo Português de Hipercolesterolemia Familiar
- Cardiovascular risk assessment of dyslipidemic children: analysis of biomarkers to identify monogenic dyslipidemiaPublication . Medeiros, A.M.; Alves, A.C.; Aguiar, P; Bourbon, M.; on behalf of the Pediatric Investigators of the Portuguese Familial Hypercholesterolemia StudyThe distinction between a monogenic dyslipidemia and a polygenic/environmental dyslipidemia is important for the cardiovascular risk assessment, counseling, and treatment of these patients. The present work aims to perform the cardiovascular risk assessment of dyslipidemic children to identify useful biomarkers for clinical criteria improvement in clinical settings. Main cardiovascular risk factors were analyzed in a cohort of 237 unrelated children with clinical diagnosis of familial hypercholesterolemia (FH). About 40% carried at least two cardiovascular risk factors and 37.6% had FH, presenting mutations in LDLR and APOB. FH children showed significant elevated atherogenic markers and lower concentration of antiatherogenic particles. Children without a molecular diagnosis of FH had higher levels of TGs, apoC2, apoC3, and higher frequency of BMI and overweight/obesity, suggesting that environmental factors can be the underlying cause of their hypercholesterolem≥ia. An apoB/apoA1 ratio ≥0.68 was identified as the best biomarker (area under the curve = 0.835) to differentiate FH from other dyslipidemias. The inclusion in clinical criteria of a higher cut-off point for LDL cholesterol or an apoB/apoA1 ratio ≥0.68 optimized the criteria sensitivity and specificity. The correct identification, at an early age, of all children at-risk is of great importance so that specific interventions can be implemented. apoB/apoA1 can improve the identification of FH patients.
- Cardiovascular risk assessment of pediatric dyslipidemic patientsPublication . Medeiros, A.M.; Alves, A.C.; Bourbon, M.Identification of young population with high cardiovascular (CV) risk allows early intervention and prevention, delaying or abolishing occurrence of CHD in adult life. Hypercholesterolemia is an important CV risk factor that can be due to environmental or genetic causes. Genetic dyslipidemias, as Familial Hypercholesterolemia (FH), are associated with major risk of CV events.
- Cardiovascular risk assessment of pediatric dyslipidemic patientsPublication . Medeiros, A.M.; Alves, A.C.; Bourbon, M.
- Cardiovascular risk estimation and management in Familial Hypercholesterolemia patientsPublication . Chora, J.R.; Medeiros, A.M.; Alves, A.C.; Bourbon, M.Objectives and study samples: - Estimate cardiovascular disease (CVD) risk; - What are the lipid-lowering therapy (LLT) strategies; - How many are reaching LDL-C targets; … in Familial Hypercholesterolemia (FH) patients and in the Portuguese general population
- Cardiovascular Risk of Children With Clinical Diagnosis of Familial HypercholesterolemiaPublication . Alves, A.C.; Medeiros, A.M.; Bourbon, M.Familial hypercholesterolemia (FH) is an inherited disorder of cholesterol metabolism, clinically characterized by high levels of LDL-associated cholesterol in plasma leading to accelerated atherosclerosis and increased risk of premature coronary heart disease (CHD). FH results from mutations in three genes involved in lipid metabolism: LDLR, APOB, PCSK9. Molecular identification of these patients can reduce the burden of mortality from cardiovascular disorders simply by the correct identification of the disease early in life, followed by counselling on appropriate lifestyle modifications and therapeutic measures when required. The aim of the Portuguese FH Study (PFHS) is to identify FH patients in order to prevent the development of premature CHD. From 563 index patients sent for the study, 153 are children. The aim of this study was to analyse the data from children with and without genetically diagnosis of FH recruited for the PFHS concerning their BMI.