SynthesisArteriosclerosis, thrombosis, and vascular biology2013
Exome sequencing and directed clinical phenotyping diagnose cholesterol ester storage disease presenting as autosomal recessive hypercholesterolemia.
Synthesis in Arteriosclerosis, thrombosis, and vascular biology, 2013. 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 28 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
28 citing papers in PubMed, 102 citations in OpenAlex.
- Should Familial Hypercholesterolaemia Be Included in the UK Newborn Whole Genome Sequencing Programme?Current atherosclerosis reports · 2023Review
- Lysosomal acid lipase deficiency: A rare inherited dyslipidemia but potential ubiquitous factor in the development of atherosclerosis and fatty liver disease.Frontiers in genetics · 2022Review
- Genetic Determinants of Plasma Low-Density Lipoprotein Cholesterol Levels: Monogenicity, Polygenicity, and "Missing" Heritability.Biomedicines · 2021Review
- Role of PCSK9 Inhibitors in Patients with Familial Hypercholesterolemia.Endocrinology and metabolism (Seoul, Korea) · 2021Article
- Cholesteryl ester storage disease of clinical and genetic characterisation: A case report and review of literature.World journal of clinical cases · 2020Article
- Review
- Functional Characterization of LIPA (Lysosomal Acid Lipase) Variants Associated With Coronary Artery Disease.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- Large-scale functional LIPA variant characterization to improve birth prevalence estimates of lysosomal acid lipase deficiency.Human mutation · 2019Article
- Evaluation of the role of STAP1 in Familial Hypercholesterolemia.Scientific reports · 2019Article
- Lysosomal Acid Lipase in Lipid Metabolism and Beyond.Arteriosclerosis, thrombosis, and vascular biology · 2019Review
- The complex molecular genetics of familial hypercholesterolaemia.Nature reviews. Cardiology · 2019Review
- Lysosomal acid lipase deficiency - early diagnosis is the key.Hepatic medicine : evidence and research · 2019Review
- Management of homozygous familial hypercholesterolaemia in two brothers.BMJ case reports · 2018Article
- The role of sebelipase alfa in the treatment of lysosomal acid lipase deficiency.Therapeutic advances in gastroenterology · 2017Review
- Genetic Architecture of Familial Hypercholesterolaemia.Current cardiology reports · 2017Review
- Novel treatment options for lysosomal acid lipase deficiency: critical appraisal of sebelipase alfa.The application of clinical genetics · 2016Review
- Genetics of Lipid and Lipoprotein Disorders and Traits.Current genetic medicine reports · 2016Review
- Lysosomal Acid Lipase Activity Is Reduced Both in Cryptogenic Cirrhosis and in Cirrhosis of Known Etiology.PloS one · 2016Article
- Clinical Features of Lysosomal Acid Lipase Deficiency.Journal of pediatric gastroenterology and nutrition · 2015Article
- Dyslipidaemia: Lysosomal acid lipase deficiency-a cautious leap forward.Nature reviews. Endocrinology · 2015Article
Corrections and comments
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Authors and funding
38 authors at 7 institutions in 4 countries.
Funding
Abstract
objectiveAutosomal recessive hypercholesterolemia is a rare inherited disorder, characterized by extremely high total and low-density lipoprotein cholesterol levels, that has been previously linked to mutations in LDLRAP1. We identified a family with autosomal recessive hypercholesterolemia not explained by mutations in LDLRAP1 or other genes known to cause monogenic hypercholesterolemia. The aim of this study was to identify the molecular pathogenesis of autosomal recessive hypercholesterolemia in this family. APPROACH AND
resultsWe used exome sequencing to assess all protein-coding regions of the genome in 3 family members and identified a homozygous exon 8 splice junction mutation (c.894G>A, also known as E8SJM) in LIPA that segregated with the diagnosis of hypercholesterolemia. Because homozygosity for mutations in LIPA is known to cause cholesterol ester storage disease, we performed directed follow-up phenotyping by noninvasively measuring hepatic cholesterol content. We observed abnormal hepatic accumulation of cholesterol in the homozygote individuals, supporting the diagnosis of cholesterol ester storage disease. Given previous suggestions of cardiovascular disease risk in heterozygous LIPA mutation carriers, we genotyped E8SJM in >27 000 individuals and found no association with plasma lipid levels or risk of myocardial infarction, confirming a true recessive mode of inheritance.
conclusionsBy integrating observations from Mendelian and population genetics along with directed clinical phenotyping, we diagnosed clinically unapparent cholesterol ester storage disease in the affected individuals from this kindred and addressed an outstanding question about risk of cardiovascular disease in LIPA E8SJM heterozygous carriers.
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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.