142 documents found, page 1 of 15
Regulatory Variants In LDLR And PCSK9 Promoters And 5'UTRs: Investigating The i...
Graça, R.; Menezes, J.; Fernandes, R.; Alves, A.C.; Romão, L.; Bourbon, M.Background and Aims: Familial Hypercholesterolaemia (FH) is a genetic disorder of lipid metabolism caused by pathogenic variants in LDLR, APOB, and PCSK9. While diagnostic efforts traditionally focus on coding variants, non-coding regions, such as promoters and 5'UTRs, remain understudied despite their importance. This work aims to characterise 100 variants in the promotor/5'UTR of LDLR and PCSK9. Methods: The ...
To Correct or not to Correct (for treatment): Estimating Pre-treatment LDL-C Co...
Stevens, C.A.T.; Elshorbagy, A.; Vallejo-Vaz, A.J.; Dharmayat, K.; Lyons, A.; Bourbon, M.; Chora, J.; Humphries, S.E.; Catapano, A.L.; Hovingh, G.Background and Aims: Pretreatment LDL-C measurements aid familial hypercholesterolaemia (FH) diagnosis, and are crucial in epidemiologic studies investigating FH, but are often unavailable because individuals are already on lipid-lowering medication (LLM). Several formulae have been reported to estimate pre-treatment LDL-C in people on LLM by ‘correcting’ their LDL-C concentrations for LLM type and dosage, base...
Resolving conflicting LDLR variants in ClinVar - Progress of the ClinGen famili...
Chora, J.; Iacocca, M.; Elnagheeb, M.; Kullo, I.; Bourbon, M.; on behalf of the ClinGen FH VCEPFamilial hypercholesterolemia (FH) is the most common monogenic disorder of lipid metabolism. Genetic testing can confirm the clinical diagnosis, but there are currently over 3300 different variants in LDLR deposited in ClinVar and ~400 had conflicting classifications of pathogenicity. Here, we present the progress of LDLR variant classification by the FH Variant Curation Expert Panel (VCEP), composed of 13 rev...
Next Generation Sequencing – a key tool for diagnosis of Familial Dyslipidemias
Miranda, B.; Alves, A.C.; Bourbon, M.Dyslipidemia, a clinical condition defined by abnormal lipid concentrations in blood, can have a genetic etiology. Familial dyslipidemias are a group of genetic diseases, the majority being rare, associated with several serious conditions. Raised triglyceride levels are associated with pancreatic/hepatic complications. Elevated cholesterol levels promote atherosclerosis and increase patients' cardiovascular ris...
Portuguese Familial Hypercholesterolemia Study as the basis of APOB Variants Da...
Ferreira, M.; Chora, J.R.; Medeiros, A.M.; Bourbon, M.; Alves, A.C.Familial hypercholesterolemia (FH) is na autosomal semi dominant disorder of lipid metabolismo associated with increased cardiovascular risk. The genetic diagnosis of FH is usually based on the analysis of three main genes: LDLR, APOB, and PCSK9. APOB variants are responsible for about 5%-10% of FH cases and in the last years, the whole gene has been sequenced due to next generation sequencing (NGS), increasing...
Familial hypercholesterolemia in Portugal - lipid-lowering strategies and cardi...
Chora, J.R.; Medeiros, A.M.; Alves, A.C.; Bourbon, M.Aims 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.
Extended next-generation sequencing panel for Familial Hypercholesterolemia
Medeiros, A.M.; Alves, A.C.; Bourbon, M.Familial Hypercholesterolemia (FH) is a common autosomal genetic disorder (1/250-1/500 worldwide). Clinically these patients present with high levels of cholesterol since birth, family history of hypercholesterolemia and premature cardiovascular disease. Formal genetic diagnosis includes the study of 3 genes: LDLR, APOB, PCSK9. Recently, other 5 genes have been associated with the FH phenotype (LDLRAP1, APOE, L...
Familial Hypercholesterolemia Monogenic Polygenic or Both
Medeiros, A.M.; Alves, A.C.; Chora, J.R.; Bourbon, M.The present work aims to determine the genetic cause (monogenic or polygenic) of hypercholesterolemia in clinical FH patients.
miRNA target-binding sites as regulators of genes involved in the lipid metabol...
Medeiros, A.M.; Enguita, F.J.; Bourbon, M.Aims to analyze miRNAs target sites as regulators of genes involved in the lipid metabolism in FH mutation-negative patients.
Case-level data sharing makes a difference in variant classification
Chora, J.R.; Tichý, L.; Lacocca, M.A.; Freiberger, T.; Bourbon, M.The American College of Medical Genetics and Genomics guidelines for variant classification are composed of several evidence criteria that, when combined, lead to a 5-tier pathogenicity variant classification. Several criteria rely on case-level data from patients, relatives, or controls with or without a particular variant of interest. (...)