ArticleGenetics in medicine : official journal of the American College of Medical Genetics2018
Analysis of publicly available LDLR, APOB, and PCSK9 variants associated with familial hypercholesterolemia: application of ACMG guidelines and implications for familial hypercholesterolemia diagnosis.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 150 citations in OpenAlex.
- A randomized controlled trial of genetic testing and cascade screening in familial hypercholesterolemia.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Trial
- Functional Analysis of LDLR (Low-Density Lipoprotein Receptor) Variants in Patient Lymphocytes to Assess the Effect of Evinacumab in Homozygous Familial Hypercholesterolemia Patients With a Spectrum of LDLR Activity.Arteriosclerosis, thrombosis, and vascular biology · 2019Trial
- LDL hypercholesterolemia in children: genetic influence and response to lifestyle advice - follow-up of the Fr1dolin-trial.Lipids in health and disease · 2026Article
- Proposal of a familial hypercholesterolemia paediatric diagnostic score (FH-PeDS).European journal of preventive cardiology · 2026Article
- Review
- Cascade screening and genetic variant pathogenicity assessment for familial hypercholesterolemia in a township‑based elderly population.Lipids in health and disease · 2026Article
- Integrated Clinical, Molecular, and Machine Learning Assessment of Familial Hypercholesterolemia.Life (Basel, Switzerland) · 2026Article
- In Reply.Deutsches Arzteblatt international · 2026Article
- Real-world effectiveness and cardiovascular outcomes of PCSK9 inhibitor therapy: a prospective registry study.Lipids in health and disease · 2026 · on this mapArticle
- Article
- Review
- Population Admixture andJournal of cardiovascular development and disease · 2026Article
- Functional analysis from ex-vivo characterization of LDLR exon 13-15 duplication associated to familial hypercholesterolemia.Frontiers in endocrinology · 2026Article
- Article
- Lipidomic Signature of Patients with Familial Hypercholesterolemia Carrying Pathogenic Variants Unveils a Cue of Increased Cardiovascular Risk.International journal of molecular sciences · 2025Article
- Optimization of multi-ancestry polygenic risk score disease prediction models.Scientific reports · 2025Article
- Article
- Functional Testing of Familial Hypercholesterolemia-Related Variants: From Bench to Clinics.JACC. Basic to translational science · 2025Article
- GeneCOCOA: Detecting context-specific functions of individual genes using co-expression data.PLoS computational biology · 2025Article
- Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.