Imperial College London
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ProfessorGrahamWilliams

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Clinical Professor of Endocrinology
 
 
 
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Contact

 

+44 (0)20 3313 1383graham.williams

 
 
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Location

 

10N5Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Formosa:2021:10.3389/fendo.2021.709711,
author = {Formosa, MM and Bergen, DJM and Gregson, CL and Maurizi, A and Kämpe, A and Garcia-Giralt, N and Zhou, W and Grinberg, D and Ovejero, Crespo D and Zillikens, MC and Williams, GR and Bassett, JHD and Brandi, ML and Sangiorgi, L and Balcells, S and Högler, W and Van, Hul W and Mäkitie, O},
doi = {10.3389/fendo.2021.709711},
journal = {Frontiers in Endocrinology},
pages = {1--24},
title = {A Roadmap to gene discoveries and novel therapies in monogenic low and high bone mass disorders},
url = {http://dx.doi.org/10.3389/fendo.2021.709711},
volume = {12},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Genetic disorders of the skeleton encompass a diverse group of bone diseases differing in clinical characteristics, severity, incidence and molecular etiology. Of particular interest are the monogenic rare bone mass disorders, with the underlying genetic defect contributing to either low or high bone mass phenotype. Extensive, deep phenotyping coupled with high-throughput, cost-effective genotyping is crucial in the characterization and diagnosis of affected individuals. Massive parallel sequencing efforts have been instrumental in the discovery of novel causal genes that merit functional validation using in vitro and ex vivo cell-based techniques, and in vivo models, mainly mice and zebrafish. These translational models also serve as an excellent platform for therapeutic discovery, bridging the gap between basic science research and the clinic. Altogether, genetic studies of monogenic rare bone mass disorders have broadened our knowledge on molecular signaling pathways coordinating bone development and metabolism, disease inheritance patterns, development of new and improved bone biomarkers, and identification of novel drug targets. In this comprehensive review we describe approaches to further enhance the innovative processes taking discoveries from clinic to bench, and then back to clinic in rare bone mass disorders. We highlight the importance of cross laboratory collaboration to perform functional validation in multiple model systems after identification of a novel disease gene. We describe the monogenic forms of rare low and high rare bone mass disorders known to date, provide a roadmap to unravel the genetic determinants of monogenic rare bone mass disorders using proper phenotyping and genotyping methods, and describe different genetic validation approaches paving the way for future treatments.
AU  - Formosa,MM
AU  - Bergen,DJM
AU  - Gregson,CL
AU  - Maurizi,A
AU  - Kämpe,A
AU  - Garcia-Giralt,N
AU  - Zhou,W
AU  - Grinberg,D
AU  - Ovejero,Crespo D
AU  - Zillikens,MC
AU  - Williams,GR
AU  - Bassett,JHD
AU  - Brandi,ML
AU  - Sangiorgi,L
AU  - Balcells,S
AU  - Högler,W
AU  - Van,Hul W
AU  - Mäkitie,O
DO  - 10.3389/fendo.2021.709711
EP  - 24
PY  - 2021///
SN  - 1664-2392
SP  - 1
TI  - A Roadmap to gene discoveries and novel therapies in monogenic low and high bone mass disorders
T2  - Frontiers in Endocrinology
UR  - http://dx.doi.org/10.3389/fendo.2021.709711
UR  - https://www.frontiersin.org/articles/10.3389/fendo.2021.709711/full
UR  - http://hdl.handle.net/10044/1/91264
VL  - 12
ER  -
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