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Lookup NU author(s): Dr Ella Dennis,
Professor Michael Briggs
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2020 The Authors. Developmental Dynamics published by Wiley Periodicals LLC on behalf of American Association of Anatomists. For the vast majority of the 6000 known rare disease the pathogenic mechanisms are poorly defined and there is little treatment, leading to poor quality of life and high healthcare costs. Genetic skeletal diseases (skeletal dysplasias) are archetypal examples of rare diseases that are chronically debilitating, often life-threatening and for which no treatments are currently available. There are more than 450 unique phenotypes that, although individually rare, have an overall prevalence of at least 1 per 4000 children. Multiple epiphyseal dysplasia (MED) is a clinically and genetically heterogeneous disorder characterized by disproportionate short stature, joint pain, and early-onset osteoarthritis. MED is caused by mutations in the genes encoding important cartilage extracellular matrix proteins, enzymes, and transporter proteins. Recently, through the use of various cell and mouse models, disease mechanisms underlying this diverse phenotypic spectrum are starting to be elucidated. For example, ER stress induced as a consequence of retained misfolded mutant proteins has emerged as a unifying disease mechanisms for several forms of MED in particular and skeletal dysplasia in general. Moreover, targeting ER stress through drug repurposing has become an attractive therapeutic avenue.
Author(s): Dennis EP, Greenhalgh-Maychell PL, Briggs MD
Publication type: Review
Publication status: Published
Journal: Developmental Dynamics
Print publication date: 01/03/2021
Online publication date: 07/07/2020
Acceptance date: 02/07/2020
ISSN (print): 1058-8388
ISSN (electronic): 1097-0177
Publisher: John Wiley and Sons Inc.
PubMed id: 32633442