8 documents found, page 1 of 1
The Functional Landscape Of Coding Variation In The Familial Hypercholesterolem...
Tabet, Daniel R.; Coté, Atina G.; Lancaster, Megan C.; Weile, Jochen; Rayhan, Ashyad; Fotiadou, Iosifina; Kishore, Nishka; Li, Roujia; Kuang, DaVariants in the familial hypercholesterolemia gene -the most important genetic driver of cardiovascular disease-can raise circulating low-density lipoprotein (LDL) cholesterol concentrations and increase the risk of premature atherosclerosis. Definitive classifications are lacking for nearly half of clinically encountered missense variants, limiting interventions that reduce disease burden. Here, we tested the ...
Worldwide experience of homozygous familial hypercholesterolaemia: retrospectiv...
Tromp, Tycho R.; Hartgers, Merel L.; Hovingh, G Kees; Vallejo-Vaz, Antonio J.; Ray, Kausik K.; Soran, Handrean; Freiberger, Tomas; Bertolini, StefanoBackground: Homozygous familial hypercholesterolaemia (HoFH) is a rare inherited disorder resulting in extremely elevated low-density lipoprotein cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Current guidance about its management and prognosis stems from small studies, mostly from high-income countries. The objective of this study was to assess the clinical and genetic charact...
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...
Specification of ACMG AMP Guidelines for Variant Interpretation in Familial Hyp...
Chora, Joana R.; Lacocca, Michael A.; Carrié, Alain; Leigh, Sarah E.; Tichý, Lukáš; Kurtz, C. Lisa; Freiberger, Tomas; Sijbrands, Eric J.Background and Aims: the general ACMG/AMP guidelines for standardized variant interpretation in Mendelian disorders are a great asset in determining variants’ pathogenicity, but need to be adapted to each specific gene and disease.
Familial hypercholesterolemia-associated variants submitted to ClinVar: a ClinG...
Rita Chora, Joana; Iacocca, Michael A.; DiStefano, Marina T.; Carrie, Alain; Freiberger, Tomas; Leigh, Sarah E.; Kurtz, C. Lisa; Defesche, JoepFamilial hypercholesterolemia (FH) is an autosomal dominant disorder of lipid metabolism characterized by elevated levels of LDL-C and increased cardiovascular risk. A vast number of potentially pathogenic variants have been identified in FH patients in LDLR, APOB, and PCSK9 genes. We sought to encourage FH researchers/clinicians worldwide to submit their variant findings to the centralized ClinVar database, wi...
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.
Progress in ACMG/AMP-adapted guidelines for standardized variant curation in fa...
Iacocca, Michael A.; Chora, Joana; Rivera, E. Andy; DiStefano, Marina T.; Carrie, Alain; Sijbrands, Eric J.; Defesche, Joep; Freiberger, TomasBackground: - 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 gui...