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

de Vos, I.J.H.M. and Wong, A.S.W. and Welting, T.J.M. and Coull, B.J. and van Steensel, M.A.M. (2019) Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling. American Journal of Medical Genetics, Part A, 179 (8). pp. 1652-1664. ISSN 1552-4825

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Abstract

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 features of 63 previously reported patients with an SH3PXD2B, MMP14, or MMP2 mutation, demonstrating considerable clinical overlap between FTHS, WS, and MONA. Interestingly, the protein products of SH3PXD2B, MMP14, and MMP2 directly cooperate in collagen remodeling. We review animal models for these three disorders that accurately reflect the major clinical features and likewise show significant phenotypical similarity with each other. Furthermore, they demonstrate that defective collagen remodeling is central in the underlying pathology. As such, we propose a nosological revision, placing these SH3PXD2B, MMP14, and MMP2 related syndromes in a novel “defective collagen-remodelling spectrum (DECORS)”. In our opinion, this revised nosology better reflects the central role for impaired collagen remodeling, a potential target for pharmaceutical intervention.

Item Type:
Journal Article
Journal or Publication Title:
American Journal of Medical Genetics, Part A
Additional Information:
This is the peer reviewed version of the following article: Vos, IJHM, Wong, ASW, Welting, TJM, Coull, BJ, Steensel, MAM. Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling. Am J Med Genet Part A. 2019; 179A: 1652– 1664. https://doi.org/10.1002/ajmg.a.61264 which has been published in final form at https://onlinelibrary.wiley.com/doi/full/10.1002/ajmg.a.61264 This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2700/2716
Subjects:
ID Code:
135430
Deposited By:
Deposited On:
28 Aug 2019 13:10
Refereed?:
Yes
Published?:
Published
Last Modified:
14 Jul 2020 08:02