Dylan J.M. Bergen PhD,Antonio Maurizi PhD,Melissa M. Formosa PhD,Georgina L.K. McDonald MSc,Ahmed El-Gazzar PhD,Neelam Hassan MD PhD,Maria-Luisa Brandi MD PhD,José A. Riancho MD PhD,Fernando Rivadeneira MD PhD,Evangelia Ntzani MD PhD,Emma L. Duncan MD PhD,Celia L. Gregson MD PhD,Douglas P. Kiel MD PhD,M. Carola Zillikens MD PhD,Luca Sangiorgi MD PhD,Wolfgang Högler MD PhD,Ivan Duran PhD,Outi Mäkitie MD PhD,Wim Van Hul PhD,Gretl Hendrickx PhD
First published: 26 September 2022 https://doi.org/10.1002/jbmr.4715
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.
