ArticleNature communications2018
Somatic activating mutations in MAP2K1 cause melorheostosis.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07521150 (The Role of Physiotherapy and Rehabilitation in a Patient Diagnosed With Melorheostosis), which is not on this map. Cited by 43 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.
The Role of Physiotherapy and Rehabilitation in a Patient Diagnosed With Melorheostosis: A Case Report
Who cites it
43 citing papers in PubMed, 80 citations in OpenAlex.
- Melorheostosis: A Clinical, Pathologic, and Radiologic Case Series.The American journal of surgical pathology · 2019Trial
- Melorheostotic Bone Lesions Caused by Somatic Mutations in MAP2K1 Have Deteriorated Microarchitecture and Periosteal Reaction.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Trial
- Distinct Clinical and Pathological Features of Melorheostosis Associated With Somatic MAP2K1 Mutations.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Trial
- Melorheostosis Involving the Carpal and Metacarpal Bones: Diagnostic Insights From Multimodal Imaging.Clinical case reports · 2026Article
- In Vivo Base Editing Partially Rescues Bone Dysplasia in a Mouse Model of Hutchinson-Gilford Progeria Syndrome.Aging cell · 2026Article
- A dual A-to-Y and G-to-Y base editor and a four-base concurrent hypermutator in mammalian cells.Nature communications · 2026Article
- MEK inhibitor mirdametinib promotes fracture healing in osteofibrous dysplasia RASopathy.The Journal of clinical investigation · 2026Article
- Melorheostosis: Clinical, radiological, and histopathological features with a literature review.Physiological reports · 2025Review
- Discriminating activating, deactivating and resistance variants in protein kinases.Genome medicine · 2025Article
- Melorheostosis of the Hip: A Case Report.Cureus · 2025Article
- Calvarial melorheostosis: an extremely rare case and diagnostic challenge.Skeletal radiology · 2025Article
- Developing a standard dataset in the European registries for rare endocrine and bone conditions-a Melorheostosis dataset.Orphanet journal of rare diseases · 2025Article
- Review
- Unraveling melorheostosis: insights into clinical features, diagnosis, and treatment.JBMR plus · 2025Review
- Update on the Genetics of Osteogenesis Imperfecta.Calcified tissue international · 2024Review
- [Biomolecules · 2024Review
- Melorheostosis of the cervical and cervicothoracic spine: review of the literature and presentation of 3 new cases.Archives of orthopaedic and trauma surgery · 2024Review
- Aneurysmal bone cyst-like changes developed in melorheostosis with epiphyseal osteopoikilosis.Skeletal radiology · 2024Article
- The IFITM5 mutation in osteogenesis imperfecta type V is associated with an ERK/SOX9-dependent osteoprogenitor differentiation defect.The Journal of clinical investigation · 2024Article
- Precise Readout of MEK1 Proteoforms upon MAPK Pathway Modulation by Individual Ion Mass Spectrometry.Analytical chemistry · 2024Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
Melorheostosis is a sporadic disease of uncertain etiology characterized by asymmetric bone overgrowth and functional impairment. Using whole exome sequencing, we identify somatic mosaic MAP2K1 mutations in affected, but not unaffected, bone of eight unrelated patients with melorheostosis. The activating mutations (Q56P, K57E and K57N) cluster tightly in the MEK1 negative regulatory domain. Affected bone displays a mosaic pattern of increased p-ERK1/2 in osteoblast immunohistochemistry. Osteoblasts cultured from affected bone comprise two populations with distinct p-ERK1/2 levels by flow cytometry, enhanced ERK1/2 activation, and increased cell proliferation. However, these MAP2K1 mutations inhibit BMP2-mediated osteoblast mineralization and differentiation in vitro, underlying the markedly increased osteoid detected in affected bone histology. Mosaicism is also detected in the skin overlying bone lesions in four of five patients tested. Our data show that the MAP2K1 oncogene is important in human bone formation and implicate MEK1 inhibition as a potential treatment avenue for melorheostosis.
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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.