Distinct Clinical and Pathological Features of Melorheostosis Associated With Somatic MAP2K1 Mutations.
BONE AND SKIN BIOPSIES
DRIPPING CANDLE-WAX
HISTOLOGY
HYPEROSTOSIS
Journal
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
ISSN: 1523-4681
Titre abrégé: J Bone Miner Res
Pays: United States
ID NLM: 8610640
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
26
03
2018
revised:
02
08
2018
accepted:
16
08
2018
pubmed:
24
8
2018
medline:
9
4
2020
entrez:
24
8
2018
Statut:
ppublish
Résumé
Melorheostosis is a rare hyperostotic disease of the long bones classically characterized by a "dripping candle-wax" radiographic appearance. We recently described somatic activating mutations in MAP2K1 as a cause of melorheostosis. Here, we report distinguishing characteristics of patients with MAP2K1-positive melorheostosis. Fifteen unrelated patients with radiographic appearance of melorheostosis underwent paired biopsies of affected and unaffected bone for whole-exome sequencing, histology, and cell culture. Eight patients with mutations in MAP2K1 in affected bone were compared to the seven MAP2K1-negative patients to identify distinguishing characteristics. Patients with MAP2K1-positive melorheostosis had a distinct phenotype with classic "dripping candle-wax" appearance on radiographs (p = 0.01), characteristic vascular lesions on skin overlying affected bone (p = 0.01), and higher prevalence of extraosseous mineralization and joint involvement (p = 0.04 for both). Melorheostotic bone from both MAP2K1-positive and MAP2K1-negative patients showed two zones of distinct morphology-an outer segment of parallel layers of primary lamellar bone and a deeper zone of intensely remodeled highly porous osteonal-like bone. Affected bone from MAP2K1-positive patients showed excessive osteoid (p = 0.0012), increased number of osteoblasts (p = 0.012) and osteoclasts (p = 0.04), and increased vascularity on histology in comparison to paired unaffected bone which was not seen in affected bone in most MAP2K1-negative patients. The identification of a distinct phenotype of patients with MAP2K1-positive melorheostosis demonstrates clinical and genetic heterogeneity among patients with the disease. Further studies are needed to better understand the underlying pathophysiology and associated skin findings. © 2018 American Society for Bone and Mineral Research.
Identifiants
pubmed: 30138550
doi: 10.1002/jbmr.3577
pmc: PMC7577747
mid: NIHMS1633932
doi:
Substances chimiques
MAP Kinase Kinase 1
EC 2.7.12.2
MAP2K1 protein, human
EC 2.7.12.2
Banques de données
ClinicalTrials.gov
['NCT02504879']
Types de publication
Clinical Trial
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
145-156Subventions
Organisme : Intramural NIH HHS
ID : ZIA HD008973
Pays : United States
Informations de copyright
© 2018 American Society for Bone and Mineral Research.
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