8 documents found, page 1 of 1
Overweight, Obesity, And Cardiovascular Disease In Heterozygous Familial Hyperc...
Elshorbagy, Amany; Vallejo-Vaz, Antonio J.; Barkas, Fotios; Lyons, Alexander R.M.; Stevens, Christophe A.T.; Dharmayat, Kanika I.; Catapano, Alberico L.Background and aims: Overweight and obesity are modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD) in the general population, but their prevalence in individuals with heterozygous familial hypercholesterolaemia (HeFH) and whether they confer additional risk of ASCVD independent of LDL cholesterol (LDL-C) remains unclear. Methods: Cross-sectional analysis was conducted in 35 540 patients ...
Proposal of a Familial Hypercholesterolemia Pediatric Diagnostic Score (FH-PeDS)
Kafol, Jan; Miranda, Beatriz; Sikonja, Rok; Sikonja, Jaka; Wiegman, Albert; Medeiros, Ana Margarida; Alves, Ana Catarina; Freiberger, TomasBackground and aims: Familial hypercholesterolemia (FH) significantly increases cardiovascular risk from childhood yet remains widely underdiagnosed. This cross-sectional study aimed to evaluate existing pediatric FH diagnostic criteria in real-world cohorts and to develop two novel diagnostic tools: a semi-quantitative scoring system (FH-PeDS) and a machine learning model (ML-FH-PeDS) to enhance early FH detec...
The Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia Variant Cu...
Chora, Joana R.; Iacocca, Michael A.; Tichý, Lukáš; Wand, Hannah; Kurtz, C. Lisa; Zimmermann, Heather; Leon, Annette; Williams, MaggiePurpose: In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published consensus standardized guidelines for sequence-level variant classification in Mendelian disorders. To increase accuracy and consistency, the Clinical Genome Resource Familial Hypercholesterolemia (FH) Variant Curation Expert Panel was tasked with optimizing the existing ACM...
Comparison of the mutation spectrum and association with pre and post treatment...
Futema, Marta; Ramaswami, Uma; Tichy, Lukas; Bogsrud, Martin P.; Holven, Kirsten B.; Roeters van Lennep, Jeanine; Wiegman, Albert; Descamps, Olivier S.Background and aims: Familial hypercholesterolaemia (FH) is commonly caused by mutations in the LDLR, APOB or PCSK9 genes, with untreated mean low density lipoprotein-cholesterol (LDL-C) concentrations being elevated in APOB mutation carriers, even higher in LDLR mutation and highest in those with a PCSK9 mutation. Here we examine this in children with FH from Norway, UK, The Netherlands, Belgium, Czech Republi...
Comparison of the characteristics at diagnosis and treatment of children with h...
Ramaswami, Uma; Futema, Marta; Bogsrud, Martin P.; Holven, Kirsten B.; Roeters van Lennep, Jeanine; Wiegman, Albert; Descamps, Olivier S.Background and aims: For children with heterozygous familial hypercholesterolaemia (HeFH), European guidelines recommend consideration of statin therapy by age 8-10 years for those with a low density lipoprotein cholesterol (LDL-C) >3.5 mmol/l, and dietary and lifestyle advice. Here we compare the characteristics and lipid levels in HeFH children from Norway, UK, Netherlands, Belgium, Czech Republic, Austria, P...
ClinVar database of global familial hypercholesterolemia-associated DNA variants
Iacocca, Michael A.; Chora, Joana R.; Carrié, Alain; Freiberger, Tomáš; Leigh, Sarah E.; Defesche, Joep C.; Kurtz, C. Lisa; DiStefano, Marina T.Accurate and consistent variant classification is imperative for incorporation of rapidly developing sequencing technologies into genomic medicine for improved patient care. An essential requirement for achieving standardized and reliable variant interpretation is data sharing, facilitated by a centralized open-source database. Familial hypercholesterolemia (FH) is an exemplar of the utility of such a resource:...
Familial hypercholesterolemiaassociated variants in ClinVar
Chora, Joana R.; Iacocca, Michael A.; Carrié, Alain; Freiberger, Tomáš; Leigh, Sarah E.; Defesche, Joep C.; Kurtz, C. Lisa; DiStefano, Marina T.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 if untreated; High heterozygote prevalence (1/250-500); Homozygous rare (1/300 000-1 000 000); Caused by pathogenic variants in LDLR (>90%), APOB (5-10%) and PCSK9 (1-3%) genes.
Clinical utility of the polygenic LDL-C SNP score in familial hypercholesterolemia
Futema, Marta; Bourbon, Mafalda; Williams, Maggie; Humphries, Steve E.Mutations in any of three genes (LDLR, APOB and PCSK9) are known to cause autosomal dominant FH, but a mutation can be found in only ∼40% of patients with a clinical diagnosis of FH. In the remainder, a polygenic aetiology may be the cause of the phenotype, due to the co-inheritance of common LDL-C raising variants. In 2013, we reported the development of a 12-SNP LDL-C "SNP-Score" based on common variants iden...