ArticleHuman molecular genetics2014
Multilineage somatic activating mutations in HRAS and NRAS cause mosaic cutaneous and skeletal lesions, elevated FGF23 and hypophosphatemia.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03581591 (An Open Label Trial to Assess the Safety and Efficacy of Burosumab), which is not on this map. Cited by 60 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.
An Open Label Trial to Assess the Safety and Efficacy of Burosumab (KRN23), an Investigational Antibody to FGF23, in a Single Pediatric Patient With Epidermal Nevus Syndrome(ENS) and Associated Hypophosphatemic Rickets
Who cites it
60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 135 citations in OpenAlex.
- Schimmelpenning-Feuerstein-Mims syndrome: a systematic review of clinical cases to identify genotype-phenotype associations.Frontiers in medicine · 2025Pooled it
- Cancer in Multilineage Mosaic RASopathies due to Pathogenic Variants in HRAS or KRAS: A Systematic Review and Meta-analysis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Pooled it
- In Vivo Base Editing Partially Rescues Bone Dysplasia in a Mouse Model of Hutchinson-Gilford Progeria Syndrome.Aging cell · 2026Article
- When X Does Not Mark the Spot: Autosomal Dominant and Recessive Forms of Renal Hypophosphatemic Rickets and Osteomalacia.Current osteoporosis reports · 2026Review
- Hypophosphatemic rickets: diagnosis and treatment.Archives of endocrinology and metabolism · 2026Review
- Burosumab treatment in an adult with FGF23-mediated hypophosphatemia due to cutaneous skeletal hypophosphatemia syndrome.Journal of the Endocrine Society · 2026Article
- Lysophosphatidic Acid Synergizes With 1,25-Dihydroxyvitamin D to Promote Fibroblast Growth Factor-23 Synthesis via MAPK Signaling and Induction of the IL12A Gene.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Diagnosis and Management of Hypophosphatemic Disorders.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2025Review
- Targeted treatment of hypophosphatemia with trametinib in HRAS-related mosaic RASopathy.Orphanet journal of rare diseases · 2025Article
- A Child with Cutaneous-Skeletal Hypophosphatemia Syndrome Caused by a Mosaic HRAS Mutation: Outcome of Treatment with Anti-FGF23 Antibody.Calcified tissue international · 2025Article
- Treatment Advances in Tumor-Induced Osteomalacia.Calcified tissue international · 2025Review
- Exploring New Drug Repurposing Opportunities for MEK Inhibitors in RASopathies: A Comprehensive Review of Safety, Efficacy, and Future Perspectives of Trametinib and Selumetinib.Life (Basel, Switzerland) · 2024Review
- Phosphaturic mesenchymal tumor: two cases highlighting differences in clinical and radiologic presentation.Skeletal radiology · 2024Article
- Acquired Forms of Fibroblast Growth Factor 23-Related Hypophosphatemic Osteomalacia.Endocrinology and metabolism (Seoul, Korea) · 2024Review
- Burosumab for the treatment of cutaneous-skeletal hypophosphatemia syndrome.Bone reports · 2024Article
- Expansion of the complex genotypic and phenotypic spectrum of FGFR2-associated neurocutaneous syndromes.Human genetics · 2024Article
- Murine models of HRAS-mediated cutaneous skeletal hypophosphatemia syndrome suggest bone as the FGF23 excess source.The Journal of clinical investigation · 2023Article
- Case Report: Sequential postzygoticFrontiers in genetics · 2023Article
- Approach to Hypophosphatemic Rickets.The Journal of clinical endocrinology and metabolism · 2022Article
- Successful treatment with MEK-inhibitor in a patient with NRAS-related cutaneous skeletal hypophosphatemia syndrome.Genes, chromosomes & cancer · 2022Article
Corrections and comments
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Authors and funding
24 authors at 13 institutions in 2 countries.
Funding
Abstract
Pathologically elevated serum levels of fibroblast growth factor-23 (FGF23), a bone-derived hormone that regulates phosphorus homeostasis, result in renal phosphate wasting and lead to rickets or osteomalacia. Rarely, elevated serum FGF23 levels are found in association with mosaic cutaneous disorders that affect large proportions of the skin and appear in patterns corresponding to the migration of ectodermal progenitors. The cause and source of elevated serum FGF23 is unknown. In those conditions, such as epidermal and large congenital melanocytic nevi, skin lesions are variably associated with other abnormalities in the eye, brain and vasculature. The wide distribution of involved tissues and the appearance of multiple segmental skin and bone lesions suggest that these conditions result from early embryonic somatic mutations. We report five such cases with elevated serum FGF23 and bone lesions, four with large epidermal nevi and one with a giant congenital melanocytic nevus. Exome sequencing of blood and affected skin tissue identified somatic activating mutations of HRAS or NRAS in each case without recurrent secondary mutation, and we further found that the same mutation is present in dysplastic bone. Our finding of somatic activating RAS mutation in bone, the endogenous source of FGF23, provides the first evidence that elevated serum FGF23 levels, hypophosphatemia and osteomalacia are associated with pathologic Ras activation and may provide insight in the heretofore limited understanding of the regulation of FGF23.
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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.