ArticleBone2017
Melorheostosis: Exome sequencing of an associated dermatosis implicates postzygotic mosaicism of mutated KRAS.
Article in Bone, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 42 citations in OpenAlex.
- 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
- Modified criteria for identifying elevated bone mass.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025Article
- Unraveling melorheostosis: insights into clinical features, diagnosis, and treatment.JBMR plus · 2025Review
- High Bone Mass Disorders: New Insights From Connecting the Clinic and the Bench.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Review
- Case Report: Sequential postzygoticFrontiers in genetics · 2023Article
- Clinical characteristics of 10 Chinese patients with melorheostosis and identification of a somatic MAP2K1 variant in one case.Molecular genetics & genomic medicine · 2022Article
- Somatic SMAD3-activating mutations cause melorheostosis by up-regulating the TGF-β/SMAD pathway.The Journal of experimental medicine · 2020Article
- Spinal Melorheostosis: A Rare Cause for Thoracic Radiculopathy.International journal of spine surgery · 2020Article
- Clinical Evaluation of Melorheostosis in the Context of a Natural History Clinical Study.JBMR plus · 2019Article
- A postzygotic KRAS mutation in a patient with Schimmelpenning syndrome presenting with lipomatosis, renovascular hypertension, and diabetes mellitus.Journal of human genetics · 2019Article
- High Fidelity of Mouse Models Mimicking Human Genetic Skeletal Disorders.Frontiers in endocrinology · 2019Review
- CT analysis of anatomical distribution of melorheostosis challenges the sclerotome hypothesis.Bone · 2018Article
- Human Genetics of Sclerosing Bone Disorders.Current osteoporosis reports · 2018Review
- Somatic activating mutations in MAP2K1 cause melorheostosis.Nature communications · 2018Article
- Melorheostosis: a Rare Sclerosing Bone Dysplasia.Current osteoporosis reports · 2017Review
- Late-Onset Melorheostosis: A Case Report.Case reports in oncologyArticle
- Lymphatic Malformation Responsive to Sirolimus in Keratinocytic Epidermal Nevus Syndrome with KRAS Mutation: A Case and Brief Literature Discussion.Case reports in dermatologyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
Melorheostosis (MEL) is the rare sporadic dysostosis characterized by monostotic or polyostotic osteosclerosis and hyperostosis often distributed in a sclerotomal pattern. The prevailing hypothesis for MEL invokes postzygotic mosaicism. Sometimes scleroderma-like skin changes, considered a representation of the pathogenetic process of MEL, overlie the bony changes, and sometimes MEL becomes malignant. Osteopoikilosis (OPK) is the autosomal dominant skeletal dysplasia that features symmetrically distributed punctate osteosclerosis due to heterozygous loss-of-function mutation within LEMD3. Rarely, radiographic findings of MEL occur in OPK. However, germline mutation of LEMD3 does not explain sporadic MEL. To explore if mosaicism underlies MEL, we studied a boy with polyostotic MEL and characteristic overlying scleroderma-like skin, a few bony lesions consistent with OPK, and a large epidermal nevus known to usually harbor a HRAS, FGFR3, or PIK3CA gene mutation. Exome sequencing was performed to ~100× average read depth for his two dermatoses, two areas of normal skin, and peripheral blood leukocytes. As expected for non-malignant tissues, the patient's mutation burden in his normal skin and leukocytes was low. He, his mother, and his maternal grandfather carried a heterozygous, germline, in-frame, 24-base-pair deletion in LEMD3. Radiographs of the patient and his mother revealed bony foci consistent with OPK, but she showed no MEL. For the patient, somatic variant analysis, using four algorithms to compare all 20 possible pairwise combinations of his five DNA samples, identified only one high-confidence mutation, heterozygous KRAS Q61H (NM_033360.3:c.183A>C, NP_203524.1:p.Gln61His), in both his dermatoses but absent in his normal skin and blood. Thus, sparing our patient biopsy of his MEL bone, we identified a heterozygous somatic KRAS mutation in his scleroderma-like dermatosis considered a surrogate for MEL. This implicates postzygotic mosaicism of mutated KRAS, perhaps facilitated by germline LEMD3 haploinsufficiency, causing his MEL.
Indexed as
Identifiers
What OpenQuestion holds
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.