Browsing by Author "Chora, Joana"
Now showing 1 - 4 of 4
Results Per Page
Sort Options
- Adaptation of ACMG/AMP guidelines for variant interpretation in familial hypercholesterolemia – a ClinGen FH Expert Panel pilot studyPublication . Chora, Joana; A. Iacocca, Michael; Lisa Kurtz, C; Carrie, Alain; Tichy, Lukas; E. Leigh, Sarah; T. DiStefano, Marina; Defesche, Joep; J. Sijbrands, Eric; Freiberger, Tomas; A. Hegele, Robert; W. Knowles, Joshua; Bourbon, MafaldaFamilial hypercholesterolemia (FH) is an autosomal dominant disorder of lipid metabolism associated with premature atherosclerosis and increased cardiovascular risk. Over 3,000 variants in LDLR, APOB, and PCSK9 have been identified in FH patients; however, <10% of these have been functionally proven to cause disease. The recent ACMG/AMP guidelines for standardized variant interpretation in Mendelian disorders are being used to help further classify FH-associated variants. Despite such efforts, these existing ACMG/AMP guidelines need to be modified to become more disease-specific for FH. In 2016, the Clinical Genome Resource (ClinGen) consortium FH Expert Panel was created with the goal to develop FH-specific variant interpretation guidelines
- Cardiovascular risk and pharmacogenetics of statins in Familial HypercholesterolaemiaPublication . Chora, JoanaFamilial hypercholesterolemia is a cardiovascular disease risk condition since its characterized by elevated lipid values since childhood. In this work we stratified CVD risk in a sample of FH patients and the general population and analysed both cohorts in terms of lipid lowering therapy used and attainment of lipid therapeutic target levels. We saw that while the general population has moderate to high CVD risk, FH patients have high to very high CVD risk. Lipid target levels are not being met and the higher risk groups are the worst controlled. Additionally we studied the association between the genotype of specific statin pharmacogenetic relevant SNPs and lipid values after statin treatment and found that APOE rs7412 is associated with higher LDL values after statin treatment and failure to achieve target lipid levels. Predicting the effect of lipid lowering drugs based on the individual’s genetic background allows for appropriate therapeutic strategies, optimizing therapeutic benefits and minimizing toxicity risk in the individual patient.
- Genetic diagnosis of Familial HypercholesterolemiaPublication . Bourbon, Mafalda; Chora, Joana; Alves, Catarina
- Progress in ACMG/AMP-adapted guidelines for standardized variant curation in familial hypercholesterolemiaPublication . Iacocca, Michael A.; Chora, Joana; Rivera, E. Andy; DiStefano, Marina T.; Carrie, Alain; Sijbrands, Eric J.; Defesche, Joep; Freiberger, Tomas; Knowles, Joshua W.; Hegele, Robert A.; Bourbon, MafaldaBackground: - The successes of clinical genetics rely on accurate variant interpretation for the purpose of informing diagnosis and treatment: - However, this practice is often rudimentary and differs among diagnostic laboratories, leading to inconsistencies in pathogenicity classification; - In response, the Clinical Genome Resources (ClinGen) consortium approves expert panels to recommend disease-specific guidelines to achieve evidence-based, standardized variant curation practice. Familial Hypercholesterolemia (FH) Working Group: - FH is a prevalent monogenic disorder, affecting ~1/250 individuals; - It is characterized by extreme LDL cholesterol levels and premature atherosclerosis causing cardiovascular disease; - Genetic testing is increasingly offered worldwide as a central part of diagnosis.