ArticlePLoS genetics2022
ENPP1 variants in patients with GACI and PXE expand the clinical and genetic heterogeneity of heritable disorders of ectopic calcification.
Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 2 of them syntheses that pooled it.
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Who cites it
17 citing papers in PubMed, 2 syntheses or guidelines pooled it, 31 citations in OpenAlex.
- Pseudoxanthoma elasticum veiled as vasculitis: shedding light on an uncommon disorder and an in-depth review of the literature.Rheumatology international · 2024Pooled it
- Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification.Nature genetics · 2023Pooled it
- Pilot study to evaluate the safety and effectiveness of etidronate treatment for arterial calcification due to deficiency of CD73 (ACDC).Vascular medicine (London, England) · 2024Trial
- Long-term survival and phenotypic expansion in siblings with generalized arterial calcification of infancy.JCEM case reports · 2026Article
- Extracellular Adenosine Contributes to the Hydrogen Peroxide-Induced Calcification of Cultured Tendon Cells.Current issues in molecular biology · 2026Article
- A Fragile Phosphate/Pyrophosphate Balance: From Essential Mineralization to Rare Calcifying Diseases.Current osteoporosis reports · 2025Review
- Metabolites and metabolism in vascular calcification: links between adenosine signaling and the methionine cycle.American journal of physiology. Heart and circulatory physiology · 2024Review
- Pseudoxanthoma elasticum - Genetics, pathophysiology, and clinical presentation.Progress in retinal and eye research · 2024Review
- A Plasma Pyrophosphate Cutoff Value for Diagnosing Pseudoxanthoma Elasticum.International journal of molecular sciences · 2024Article
- The Purinergic Nature of Pseudoxanthoma Elasticum.Biology · 2024Review
- Weighing the Evidence for the Roles of Plasma Versus Local Pyrophosphate in Ectopic Calcification Disorders.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Article
- Zebrafish as a Model of Cardiac Pathology and Toxicity: Spotlight on Uremic Toxins.International journal of molecular sciences · 2023Review
- Plasma Level of Pyrophosphate Is Low in Pseudoxanthoma Elasticum Owing to Mutations in the ABCC6 Gene, but It Does Not Correlate with ABCC6 Genotype.Journal of clinical medicine · 2023Article
- Case report: A rare homozygous variation in theFrontiers in cardiovascular medicine · 2023Article
- Estimation of ENPP1 deficiency genetic prevalence using a comprehensive literature review and population databases.Orphanet journal of rare diseases · 2022Review
- Mutation update: Variants of the ENPP1 gene in pathologic calcification, hypophosphatemic rickets, and cutaneous hypopigmentation with punctate keratoderma.Human mutation · 2022Review
- Case Report and Review of Literature: Autosomal Recessive Hypophosphatemic Rickets Type 2 Caused by a Pathogenic Variant inFrontiers in endocrinology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy (GACI) are clinically distinct genetic entities of ectopic calcification associated with differentially reduced circulating levels of inorganic pyrophosphate (PPi), a potent endogenous inhibitor of calcification. Variants in ENPP1, the gene mutated in GACI, have not been associated with classic PXE. Here we report the clinical, laboratory, and molecular evaluations of ten GACI and two PXE patients from five and two unrelated families registered in GACI Global and PXE International databases, respectively. All patients were found to carry biallelic variants in ENPP1. Among ten ENPP1 variants, one homozygous variant demonstrated uniparental disomy inheritance. Functional assessment of five previously unreported ENPP1 variants suggested pathogenicity. The two PXE patients, currently 57 and 27 years of age, had diagnostic features of PXE and had not manifested the GACI phenotype. The similarly reduced PPi plasma concentrations in the PXE and GACI patients in our study correlate poorly with their disease severity. This study demonstrates that in addition to GACI, ENPP1 variants can cause classic PXE, expanding the clinical and genetic heterogeneity of heritable ectopic calcification disorders. Furthermore, the results challenge the current prevailing concept that plasma PPi is the only factor governing the severity of ectopic calcification.
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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.