ArticleJournal of medical genetics2016
Gain-of-function mutation in TRPV4 identified in patients with osteonecrosis of the femoral head.
Article in Journal of medical genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Osteonecrosis of the femoral head: genetic basis.International orthopaedics · 2019Pooled it
- 25+ Years of TRPV4: From Discovery to Translational Horizons.Research square · 2026Article
- Small molecule inhibition rescues the skeletal dysplasia phenotype of Trpv4 mutant mice.JCI insight · 2026Article
- TRPV4: A trigger of pathological RhoA activation in neurological disease.BioEssays : news and reviews in molecular, cellular and developmental biology · 2022Article
- De novoJournal of medical genetics · 2022Article
- Neuropathy-causing TRPV4 mutations disrupt TRPV4-RhoA interactions and impair neurite extension.Nature communications · 2021Article
- Exome sequencing for diagnosis of congenital hemolytic anemia.Orphanet journal of rare diseases · 2020Article
- Gene testing for osteonecrosis of the femoral head in systemic lupus erythematosus using targeted next-generation sequencing: A pilot study.World journal of clinical cases · 2020Article
- Mitigating osteonecrosis of the jaw (ONJ) through preventive dental care and understanding of risk factors.Bone research · 2020Review
- Thiemann disease and familial digital arthropathy - brachydactyly: two sides of the same coin?Orphanet journal of rare diseases · 2019Review
- TRPV4 and KRAS and FGFR1 gain-of-function mutations drive giant cell lesions of the jaw.Nature communications · 2018Article
- [Pathophysiology of aseptic femoral head necrosis: Pathogenesis and histopathological differential diagnosis].Der Orthopade · 2018Review
- TRPV4 (Transient Receptor Potential Vanilloid 4) Channel-Dependent Negative Feedback Mechanism Regulates GArteriosclerosis, thrombosis, and vascular biology · 2018Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundOsteonecrosis of the femoral head is a debilitating disease that involves impaired blood supply to the femoral head and leads to femoral head collapse.
methodsWe use whole-exome sequencing and Sanger sequencing to analyse a family with inherited osteonecrosis of the femoral head and fluorescent Ca(2+) imaging to functionally characterise the variant protein.
resultsWe report a family with four siblings affected with inherited osteonecrosis of the femoral head and the identification of a c.2480_2483delCCCG frameshift deletion followed by a c.2486T>A substitution in one allele of the transient receptor potential vanilloid 4 (TRPV4) gene. TRPV4 encodes a Ca(2+)-permeable cation channel known to play a role in vasoregulation and osteoclast differentiation. While pathogenic TRPV4 mutations affect the skeletal or nervous systems, association with osteonecrosis of the femoral head is novel. Functional measurements of Ca(2+) influx through mutant TRPV4 channels in HEK293 cells and patient-derived dermal fibroblasts identified a TRPV4 gain of function. Analysis of channel open times, determined indirectly from measurement of TRPV4 activity within a cluster of TRPV4 channels, revealed that the TRPV4 gain of function was caused by longer channel openings.
conclusionsThese findings identify a novel TRPV4 mutation implicating TRPV4 and altered calcium homeostasis in the pathogenesis of osteonecrosis while reinforcing the importance of TRPV4 in bone diseases and vascular endothelium.
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Registered trials
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