High Bone Mass Disorders: New Insights From Connecting the Clinic and the Bench. (21st October 2022)

• Record Type: Journal Article
• Authors: Bergen, Dylan J.M.; Maurizi, Antonio; Formosa, Melissa M.; McDonald, Georgina L.K.; El‐Gazzar, Ahmed; Hassan, Neelam; Brandi, Maria‐Luisa; Riancho, José A.; Rivadeneira, Fernando; Ntzani, Evangelia; Duncan, Emma L.; Gregson, Celia L.; Kiel, Douglas P.; Zillikens, M. Carola; Sangiorgi, Luca; Högler, Wolfgang; Duran, Ivan; Mäkitie, Outi; Van Hul, Wim; Hendrickx, Gretl
• Is Part Of: Journal of bone and mineral research. Volume 38:Number 2(2023)
• Page Start: 229
• Page End: 247
• Publication Date: 2022-10-21
• Subjects: DISEASES AND DISORDERS OF/RELATED TO BONE -- ANABOLICS -- THERAPEUTICS -- GENETIC ANIMAL MODELS -- ANIMAL MODELS -- CELL/TISSUE SIGNALING -- PARACRINE PATHWAYS -- GENETIC RESEARCH; Bones -- Metabolism -- Periodicals; Mineral metabolism -- Periodicals; 612.392
• DOI: 10.1002/jbmr.4715
• Languages: English
• ISSNs: 0884-0431

Abstract

ABSTRACT: Monogenic high bone mass (HBM) disorders are characterized by an increased amount of bone in general, or at specific sites in the skeleton. Here, we describe 59 HBM disorders with 50 known disease‐causing genes from the literature, and we provide an overview of the signaling pathways and mechanisms involved in the pathogenesis of these disorders. Based on this, we classify the known HBM genes into HBM (sub)groups according to uniform Gene Ontology (GO) terminology. This classification system may aid in hypothesis generation, for both wet lab experimental design and clinical genetic screening strategies. We discuss how functional genomics can shape discovery of novel HBM genes and/or mechanisms in the future, through implementation of omics assessments in existing and future model systems. Finally, we address strategies to improve gene identification in unsolved HBM cases and highlight the importance for cross‐laboratory collaborations encompassing multidisciplinary efforts to transfer knowledge generated at the bench to the clinic. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).