ArticleThe Journal of clinical investigation2018
CYP3A4 mutation causes vitamin D-dependent rickets type 3.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 116 citations in OpenAlex.
- Effect of epigenetics on vitamin D levels: a systematic review until December 2020.Archives of public health = Archives belges de sante publique · 2023Pooled it
- Vitamin D-Dependent Rickets Type 3: A Case Report and Systematic Review.Calcified tissue international · 2023Pooled it
- Genetic Variants Associated With the Biochemical Response to Vitamin D3 in the Multi-Ethnic Study of Atherosclerosis.The Journal of clinical endocrinology and metabolism · 2025Trial
- Vitamin D: Physiology, Pharmacology and Clinical Evidence for Supplementation-A Narrative Review.Basic & clinical pharmacology & toxicology · 2026Review
- The pathogenesis and intersecting mechanisms of monogenic bone mass disorders.Nature reviews. Endocrinology · 2026Review
- Transcriptomic Insights into Developmental Toxicity of Per- and polyfluoroalkyl Substances (PFAS) inEnvironment & health (Washington, D.C.) · 2026Article
- Refractory Rickets: Evaluation and Management.Indian journal of pediatrics · 2026Review
- Genetic background of infantile hypophosphatemia: a narrative review.Translational pediatrics · 2026Review
- A new metabolic path in type 3 rickets.The FEBS journal · 2026Review
- Genetic Variants Influencing Individual Vitamin D Status.Nutrients · 2025Review
- Natural Polymorphic Variants in the CYP450 Superfamily: A Review of Potential Structural Mechanisms and Functional Consequences.International journal of molecular sciences · 2025Review
- Etiology, clinical characteristics, genetic profile, and outcomes of children with refractory rickets at a referral center in India: a cohort study.Pediatric nephrology (Berlin, Germany) · 2025Article
- The Effects of Vitamin D on Muscle Strength Are Influenced by Testosterone Levels.Journal of cachexia, sarcopenia and muscle · 2025Article
- Analysis of 1,25-dihydroxyvitamin D genomic action in human enteroids and colonoids reveals multiple regulatory effects of vitamin D in human intestinal physiology.Frontiers in endocrinology · 2025Article
- Maternal loss of 24-hydroxylase causes increased intestinal calcium absorption and hypercalcemia during pregnancy but reduced skeletal resorption during lactation in mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Article
- Diagnostic approach to rickets: an Endocrine Society of Bengal (ESB) consensus statement.Annals of pediatric endocrinology & metabolism · 2024Article
- Targeting Calcitriol Metabolism in Acute Vitamin D Toxicity-A Comprehensive Review and Clinical Insight.International journal of molecular sciences · 2024Review
- Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows.Endocrine reviews · 2024Article
- Case 21-2024: A 10-Month-Old Boy with Vomiting and Hypercalcemia.The New England journal of medicine · 2024Article
- The Role of Intestinal Cytochrome P450s in Vitamin D Metabolism.Biomolecules · 2024Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 7 institutions in 3 countries.
Funding
Abstract
Genetic forms of vitamin D-dependent rickets (VDDRs) are due to mutations impairing activation of vitamin D or decreasing vitamin D receptor responsiveness. Here we describe two unrelated patients with early-onset rickets, reduced serum levels of the vitamin D metabolites 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and deficient responsiveness to parent and activated forms of vitamin D. Neither patient had a mutation in any genes known to cause VDDR; however, using whole exome sequencing analysis, we identified a recurrent de novo missense mutation, c.902T>C (p.I301T), in CYP3A4 in both subjects that alters the conformation of substrate recognition site 4 (SRS-4). In vitro, the mutant CYP3A4 oxidized 1,25-dihydroxyvitamin D with 10-fold greater activity than WT CYP3A4 and 2-fold greater activity than CYP24A1, the principal inactivator of vitamin D metabolites. As CYP3A4 mutations have not previously been linked to rickets, these findings provide insight into vitamin D metabolism and demonstrate that accelerated inactivation of vitamin D metabolites represents a mechanism for vitamin D deficiency.
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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.