Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling

  title={Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling},
  author={Ivo J. H. M. de Vos and Arnette Shi Wei Wong and Tim Welting and Barry J. Coull and Maurice A. M. van Steensel},
  journal={American Journal of Medical Genetics Part A},
  pages={1652 - 1664}
Frank‐Ter Haar syndrome (FTHS), Winchester syndrome (WS), and multicentric osteolysis, nodulosis, and arthropathy (MONA) are ultra‐rare multisystem disorders characterized by craniofacial malformations, reduced bone density, skeletal and cardiac anomalies, and dermal fibrosis. These autosomal recessive syndromes are caused by homozygous mutation or deletion of respectively SH3PXD2B (SH3 and PX Domains 2B), MMP14 (matrix metalloproteinase 14), or MMP2. Here, we give an overview of the clinical… Expand
Multicentric Osteolysis, Nodulosis, and Arthropathy in two unrelated children with matrix metalloproteinase 2 variants: Genetic-skeletal correlations
There is an emerging distinctive skeletal pattern of involvement in terms of both clinical and radiographic features of MONA syndrome, which includes age of onset and location of presenting skeletal manifestations, chronological order of joint affection, longitudinal disease progression, specifics of skeletal radiographic pathology and craniofacial features. Expand
A severe case of Frank-ter Haar syndrome and literature review: Further delineation of the phenotypical spectrum.
It is hypothesize that the alteration of podosomes function could lead to a reduction of the extra cellular matrix degradation and accumulation of the latter in the extracellular space, which might explain the coarsening of the facial features and the severe refractory glaucoma. Expand
Clinical Radiological and Molecular Profile of a Patient Affected With Multicentric Osteolysis Nodulosis and Arthropathy
The clinical and radiographic findings of a 14-year-old girl with molecularly proven MONA, who presented with painless osteolytic changes of the feet and upper extremities and developed hip arthritis are reported. Expand
A novel matrix metalloproteinase-2 mutation in two Egyptian siblings with Winchester syndrome
© 2019 Middle East Journal of Medical Genetics | Published by Wolters Kluwer ‐ Medknow DOI: 10.4103/MXE.MXE_9_19 Introduction Torg–Winchester syndrome, also termed multicentric osteolysis nodulosisExpand
The novel zebrafish model pretzel demonstrates a central role for SH3PXD2B in defective collagen remodelling and fibrosis in Frank-Ter Haar syndrome
The pretzel model presented here can be used to further delineate the underlying mechanism of the fibrosis observed in DECORS, as well as screening and subsequent development of novel drugs targeting DECORS-related fibrosis. Expand
Different roles of matrix metalloproteinase 2 in osteolysis of skeletal dysplasia and bone metastasis
The latest research on MMP2 in bone homeostasis is reviewed and the mechanisms underlying the role of this protein in skeletal metastasis and developmental osteolysis are discussed. Expand
Mitral Valve Prolapse and Its Motley Crew‐Syndromic Prevalence, Pathophysiology, and Progression of a Common Heart Condition
It is highlighted that in contrast to early studies describing MVP as a benign entity, the clinical course experienced by patients can be heterogeneous and may cause significant cardiovascular morbidity and mortality, so a review of clinical guidelines to allow for earlier surgical intervention may be warranted to lower cardiovascular risk in patients with MVP. Expand
Matrix Metalloproteinases and Glaucoma Treatment
It is hypothesized that the higher concentrations of bimatoprost achieved in ocular outflow tissues with the implant produce greater MMP upregulation and more extensive, sustained MMP-mediated target tissue remodeling, providing an extended duration of effect. Expand
MMP14 in Sarcoma: A Regulator of Tumor Microenvironment Communication in Connective Tissues
An overview of the function and regulation of M MP14 is provided and their relationship with clinical and pre-clinical MMP14 data in both adult and childhood sarcomas is discussed. Expand
MMP1 and MMP9 are potential prognostic biomarkers and targets for uveal melanoma
  • Tianyu Wang, Yuanyuan Zhang, Jianhao Bai, Yawen Xue, Qing Peng
  • Medicine
  • BMC cancer
  • 2021
The expression and prognostic value of matrix metalloproteinases (MMPs) in UVM was explored to provide potential biomarkers and targets for UVM and it was revealed that the transcriptional levels of MMP1, MMP9, M MP10, and MMP10 were upregulated in U VM tissues compared to normal tissues. Expand


Winchester syndrome caused by a homozygous mutation affecting the active site of matrix metalloproteinase 2
The clinical and molecular findings suggest that Torg, NAO and Winchester syndromes are allelic disorders that form a clinical spectrum. Expand
Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome
Two family-specific homoallelic MMP2 mutations are identified: R101H and Y244X, a nonsense mutation that effects a deletion of the substrate-binding and catalytic sites and the fibronectin type II-like and hemopexin/TIMP2 binding domains and the missense mutation that disrupts hydrogen bond formation within the highly conserved prodomain adjacent to the catalytic zinc ion. Expand
Clinical and mutation profile of multicentric osteolysis nodulosis and arthropathy
The clinical, radiographic and molecular findings in all individuals with molecularly proven MONA from the present cohort and previous reports are characterized, and a comprehensive review of the MMP2 related disorders is provided. Expand
A novel homozygous MMP2 mutation in a family with Winchester syndrome
The clinical evolution of two sisters with a Winchester phenotype is reported and a new homozygous mutation in the catalytic domain of the MMP2 gene is identified, consistent with the involvement of M MP2 in Winchester syndrome and with the hypothesis that Winchester and NAO syndromes are allelic disorders that form a continuous clinical spectrum. Expand
Multicentric osteolysis with nodulosis and arthropathy (MONA) with cardiac malformation, mimicking polyarticular juvenile idiopathic arthritis: case report and literature review
The case of a 5-year-old boy with double outlet right ventricle, ventricular septal defect, coarctation of the aorta and MONA is presented and a link between MMP2 deficiency and heart development is established, and it is suggested that all MONA patients be examined for possible cardiac defects. Expand
Inherited multicentric osteolysis with arthritis: a variant resembling Torg syndrome in a Saudi family.
The autosomal recessive inheritance, clinical, and radiologic characteristics of the affected sibs suggested that they had a form of multicentric osteolysis most closely resembling the Torg syndrome, but with a unique facial appearance, fibrocollagenous pads, and body hirsutism not noted in the original description of the syndrome. Expand
Mutation of membrane type-1 metalloproteinase, MT1-MMP, causes the multicentric osteolysis and arthritis disease Winchester syndrome.
Using cultured fibroblasts from the proband, homozygous mutations in membrane type-1 metalloproteinase (MT1-MMP or MMP14) are identified and it is demonstrated that the resulting hydrophobic-region signal-peptide substitution decreases MT1- MMP membrane localization with consequent impairment of pro-M MP2 activation, and a structure-based mechanism for this effect is proposed. Expand
Patient with Mutation in the Matrix Metalloproteinase 2 (MMP2) Gene - A Case Report and Review of the Literature
The clinical presentation of the patient included moderate osteolysis of the small joints of the hands and knees, hirsutism, nodulosis sparing the palms and soles, corneal opacities and mild facial dysmorphism without gum hypertrophy and some previously unreported endocrine manifestations such as premature thelarche and elevated follicle-stimulating hormone levels. Expand
A novel matrix metalloproteinase 2 (MMP2) terminal hemopexin domain mutation in a family with multicentric osteolysis with nodulosis and arthritis with cardiac defects
It is suggested that cardiac defects may also represent a component of this syndrome and thus a physiologically relevant target of MMP-2 activity. Expand
Loss of MMP-2 disrupts skeletal and craniofacial development and results in decreased bone mineralization, joint erosion and defects in osteoblast and osteoclast growth.
It is reported that Mmp2-/- mice display attenuated features of human MOA including progressive loss of bone mineral density, articular cartilage destruction and abnormal long bone and craniofacial development and these changes are associated with markedly and developmentally restricted decreases in osteoblast and osteoclast numbers in vivo. Expand