A Roadmap to Gene Discoveries and Novel Therapies in Monogenic Low and High Bone Mass Disorders

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dc.contributor.author GEMSTONE Working Grp 3 COST Action
dc.contributor.author Formosa, Melissa M.
dc.contributor.author Bergen, Dylan J. M.
dc.contributor.author Gregson, Celia L.
dc.contributor.author Mäkitie, Outi
dc.date.accessioned 2021-11-01T18:10:03Z
dc.date.available 2021-11-01T18:10:03Z
dc.date.issued 2021-08-13
dc.identifier.citation GEMSTONE Working Grp 3 COST Action , Formosa , M M , Bergen , D J M , Gregson , C L & Mäkitie , O 2021 , ' A Roadmap to Gene Discoveries and Novel Therapies in Monogenic Low and High Bone Mass Disorders ' , Frontiers in Endocrinology , vol. 12 , 709711 . https://doi.org/10.3389/fendo.2021.709711
dc.identifier.other PURE: 169970465
dc.identifier.other PURE UUID: 4f42c26e-5eff-4f4b-9da2-e53f9c6c2f86
dc.identifier.other WOS: 000697148700001
dc.identifier.uri http://hdl.handle.net/10138/335926
dc.description.abstract 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. en
dc.format.extent 24
dc.language.iso eng
dc.relation.ispartof Frontiers in Endocrinology
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject bone mass
dc.subject monogenic bone disorders
dc.subject gene variants
dc.subject functional validation
dc.subject drug discovery
dc.subject GEMSTONE
dc.subject skeletal dysplasia
dc.subject AUTOSOMAL-DOMINANT OSTEOPETROSIS
dc.subject ALBERS-SCHONBERG-DISEASE
dc.subject MOUSE MODELS
dc.subject OSTEOGENESIS IMPERFECTA
dc.subject BUCHEM-DISEASE
dc.subject OSTEOPOROSIS
dc.subject MUTATION
dc.subject SCLEROSTEOSIS
dc.subject LIMITATIONS
dc.subject DEFICIENCY
dc.subject 3121 General medicine, internal medicine and other clinical medicine
dc.title A Roadmap to Gene Discoveries and Novel Therapies in Monogenic Low and High Bone Mass Disorders en
dc.type Review Article
dc.contributor.organization HUS Children and Adolescents
dc.contributor.organization Clinicum
dc.contributor.organization Lastentautien yksikkö
dc.contributor.organization Children's Hospital
dc.contributor.organization CAMM - Research Program for Clinical and Molecular Metabolism
dc.contributor.organization Research Programs Unit
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.3389/fendo.2021.709711
dc.relation.issn 1664-2392
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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