ArticleJournal of medical genetics2014
Whole exome sequencing of familial hypercholesterolaemia patients negative for LDLR/APOB/PCSK9 mutations.
Article in Journal of medical genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03984149 (Prevalence and Mutation Rate of Lipa Gene in LIPIGEN Subjects With Clinical Diagnosis of FH), which is not on this map. Cited by 50 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Prevalence and Mutation Rate of Lipa Gene in LIPIGEN Subjects With Clinical Diagnosis of FH
Who cites it
50 citing papers in PubMed, 117 citations in OpenAlex.
- Genome sequencing identifies monogenic causes in adults with metabolic diseases.Journal of the Endocrine Society · 2026Article
- The COPI coatomer influences LDL receptor activity, hepatic lipid storage, and apoB secretion.bioRxiv : the preprint server for biology · 2026Article
- Genetic Determinants of the Familial Hypercholesterolaemia Phenotype.Annals of human genetics · 2025Review
- Family hypercholesterolemia due toMolecular genetics and metabolism reports · 2025Article
- Clinical exome sequencing identifies novel gene variants associated with ischemic stroke in the Saudi Tabuk population.Frontiers in human neuroscience · 2025Article
- Functional Analysis of 3'UTR Variants at theHuman mutation · 2024Article
- Genetic Characteristics of Latvian Patients with Familial Hypercholesterolemia: The First Analysis from Genome-Wide Sequencing.Journal of clinical medicine · 2023Article
- Barriers and shortcomings in access to cardiovascular management and prevention for familial hypercholesterolemia during the COVID-19 pandemic.Clinical cardiology · 2023Review
- Familial Hypercholesterolemia: Where Do We Stand?ARYA atherosclerosis · 2023Article
- Exploring the Association between Low-Density Lipoprotein Subfractions and Major Adverse Cardiovascular Outcomes-A Comprehensive Review.International journal of molecular sciences · 2023Review
- Genetic Heterogeneity of Familial Hypercholesterolemia: Repercussions for Molecular Diagnosis.International journal of molecular sciences · 2023Review
- Genetic and molecular architecture of familial hypercholesterolemia.Journal of internal medicine · 2023Review
- Whole Exome Sequencing Insufficient for a Definitive Diagnosis of a Patient with Compound Heterozygous Familial Hypercholesterolemia.Internal medicine (Tokyo, Japan) · 2022Article
- Review
- A human liver chimeric mouse model for non-alcoholic fatty liver disease.JHEP reports : innovation in hepatology · 2021Article
- Improvement of Definite Diagnosis of Familial Hypercholesterolemia Using an Expanding Genetic Analysis.JACC. Asia · 2021Article
- Genetic testing for familial hypercholesterolemia-past, present, and future.Journal of lipid research · 2021Review
- Unravelling the complex genetics of common kidney diseases: from variants to mechanisms.Nature reviews. Nephrology · 2020Review
- Genetics of Familial Hypercholesterolemia: New Insights.Frontiers in genetics · 2020Review
- Diagnosis and Treatment of Heterozygous Familial Hypercholesterolemia.Journal of the American Heart Association · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 14 institutions in 6 countries.
Funding
Abstract
backgroundFamilial hypercholesterolaemia (FH) is an autosomal dominant disease of lipid metabolism, which leads to early coronary heart disease. Mutations in LDLR, APOB and PCSK9 can be detected in 80% of definite FH (DFH) patients. This study aimed to identify novel FH-causing genetic variants in patients with no detectable mutation. METHODS AND
resultsExomes of 125 unrelated DFH patients were sequenced, as part of the UK10K project. First, analysis of known FH genes identified 23 LDLR and two APOB mutations, and patients with explained causes of FH were excluded from further analysis. Second, common and rare variants in genes associated with low-density lipoprotein cholesterol (LDL-C) levels in genome-wide association study (GWAS) meta-analysis were examined. There was no clear rare variant association in LDL-C GWAS hits; however, there were 29 patients with a high LDL-C SNP score suggestive of polygenic hypercholesterolaemia. Finally, a gene-based burden test for an excess of rare (frequency <0.005) or novel variants in cases versus 1926 controls was performed, with variants with an unlikely functional effect (intronic, synonymous) filtered out.
conclusionsNo major novel locus for FH was detected, with no gene having a functional variant in more than three patients; however, an excess of novel variants was found in 18 genes, of which the strongest candidates included CH25H and INSIG2 (p<4.3×10(-4) and p<3.7×10(-3), respectively). This suggests that the genetic cause of FH in these unexplained cases is likely to be very heterogeneous, which complicates the diagnostic and novel gene discovery process.
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Registered trials
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.