ArticleAmerican journal of human genetics2023
Bi-allelic variants in HMGCR cause an autosomal-recessive progressive limb-girdle muscular dystrophy.
Article in American journal of human genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Article
- Skeletal muscle-specific deficiency of Rab geranylgeranyl transferase beta subunit induces myopathy and exacerbates the symptoms caused by HMG-CoA reductase deficiency in mice.Molecular metabolism · 2026Article
- Reducing Body Myopathy in Female Patients WithNeurology. Genetics · 2026Article
- Balancing cholesterol metabolism in the liver and gut: perspectives in health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Expanded clinical and genetic characterization of autosomal recessive HMGCR-related muscular dystrophy.Journal of neuromuscular diseases · 2026Article
- HMGCR genetic variability in Parkinson's disease in a Spanish cohort: associations with lipid metabolism and early onset.Journal of neurology · 2025Article
- Effects of HMG CoA reductase (HMGCR) deficiency on skeletal muscle development.The FEBS journal · 2025Article
- High-Density Lipoprotein-Associated Cholesterol Abnormalities in a Clinical Outcomes Study of Dysferlin-Deficient Limb-Girdle Muscular Dystrophy Type R2.Journal of cachexia, sarcopenia and muscle · 2025Article
- HMGCS1 variants cause rigid spine syndrome amenable to mevalonic acid treatment in an animal model.Brain : a journal of neurology · 2025Article
- An update on the pathogenesis of idiopathic inflammatory myopathies.Current opinion in rheumatology · 2025Review
- Review
- GREGoR: Accelerating Genomics for Rare Diseases.ArXiv · 2024Article
- Recent Updates on the Pathogenesis of Inflammatory Myopathies.Current rheumatology reports · 2024Review
- Pathological autoantibody internalisation in myositis.Annals of the rheumatic diseases · 2024Article
- Absence of Pathogenic Mutations and Strong Association With HLA-DRB1*11:01 in Statin-Naïve Early-Onset Anti-HMGCR Necrotizing Myopathy.Neurology(R) neuroimmunology & neuroinflammation · 2024Article
- Expert panel curation of 31 genes in relation to limb girdle muscular dystrophy.Annals of clinical and translational neurology · 2024Article
- Inhibition of human mevalonate kinase by allosteric inhibitors of farnesyl pyrophosphate synthase.FEBS open bio · 2024Article
- Anti-Ku + myositis: an acquired inflammatory protein-aggregate myopathy.Acta neuropathologica · 2024Article
- Expert Panel Curation of 31 Genes in Relation to Limb Girdle Muscular Dystrophy.bioRxiv : the preprint server for biology · 2024Article
- Peroxisomal Localization of a Truncated HMG-CoA Reductase under Low Cholesterol Conditions.Biomolecules · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
30 authors at 9 institutions in 1 country.
Funding
Abstract
Statins are a mainstay intervention for cardiovascular disease prevention, yet their use can cause rare severe myopathy. HMG-CoA reductase, an essential enzyme in the mevalonate pathway, is the target of statins. We identified nine individuals from five unrelated families with unexplained limb-girdle like muscular dystrophy and bi-allelic variants in HMGCR via clinical and research exome sequencing. The clinical features resembled other genetic causes of muscular dystrophy with incidental high CPK levels (>1,000 U/L), proximal muscle weakness, variable age of onset, and progression leading to impaired ambulation. Muscle biopsies in most affected individuals showed non-specific dystrophic changes with non-diagnostic immunohistochemistry. Molecular modeling analyses revealed variants to be destabilizing and affecting protein oligomerization. Protein activity studies using three variants (p.Asp623Asn, p.Tyr792Cys, and p.Arg443Gln) identified in affected individuals confirmed decreased enzymatic activity and reduced protein stability. In summary, we showed that individuals with bi-allelic amorphic (i.e., null and/or hypomorphic) variants in HMGCR display phenotypes that resemble non-genetic causes of myopathy involving this reductase. This study expands our knowledge regarding the mechanisms leading to muscular dystrophy through dysregulation of the mevalonate pathway, autoimmune myopathy, and statin-induced myopathy.
Indexed as
Identifiers
What OpenQuestion holds
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.