TY - JOUR
T1 - Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling
AU - de Vos, Ivo J. H. M.
AU - Wong, Arnette Shi Wei
AU - Welting, Tim J. M.
AU - Coull, Barry J.
AU - van Steensel, Maurice A. M.
N1 - Funding Information:
IJHMdV is supported by the Agency for Science, Technology and Research Research Attachment Programme and together with ASWW supported by the Skin Research Institute of Singapore (IAF-PP H17/01/a0004). BJC is supported by Tenovus Scotland (T15/22 and T15/62). TJMW is supported by grants from the Dutch Arthritis Society (grants LLP14, 17-2-401, 15-3-403), STW-NWO (grant p15-23), and Stichting De Weijerhorst (grant Bewegen zonder Pijn). MAMvS is supported by SRIS, and a grant from the Biomedical Research Council, Singapore (IAF-PP H17/01/a0/008).
Publisher Copyright:
© 2019 Wiley Periodicals, Inc.
PY - 2019/8
Y1 - 2019/8
N2 - 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.
AB - 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.
KW - ECM remodeling
KW - MMP14
KW - MMP2
KW - podosomes
KW - SH3PXD2B
KW - TER HAAR SYNDROME
KW - MATRIX-METALLOPROTEINASE MT1-MMP
KW - HOMOZYGOUS MMP2 MUTATION
KW - MELNICK-NEEDLES SYNDROME
KW - EXTRACELLULAR-MATRIX
KW - CELL-SURFACE
KW - ACID MUCOPOLYSACCHARIDOSIS
KW - SKELETAL DEFORMITIES
KW - PROMMP-2 ACTIVATION
KW - WINCHESTER-SYNDROME
U2 - 10.1002/ajmg.a.61264
DO - 10.1002/ajmg.a.61264
M3 - (Systematic) Review article
C2 - 31218820
SN - 1552-4825
VL - 179
SP - 1652
EP - 1664
JO - American Journal of Medical Genetics Part A
JF - American Journal of Medical Genetics Part A
IS - 8
ER -