Assessing the contribution of genes involved in monogenic bone disorders to the etiology of atypical femoral fractures.

Autor: Garcia-Giralt N; Musculoskeletal Research Group, Hospital del Mar Research Institute, Centro de Investigación Biomédica en Red en Fragilidad y Envejecimiento Saludable (CIBERFES), ISCIII, Barcelona, Spain. ngarcia@researchmar.net., Ovejero D; Musculoskeletal Research Group, Hospital del Mar Research Institute, Centro de Investigación Biomédica en Red en Fragilidad y Envejecimiento Saludable (CIBERFES), ISCIII, Barcelona, Spain., Grinberg D; Dpt. Genetics, Microbiology and Statistics, Facultat de Biologia, IBUB, Universitat de Barcelona, Barcelona, Spain.; Centro de Investigación Biomédica en Red-Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.; Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, Spain., Nogues X; Musculoskeletal Research Group, Hospital del Mar Research Institute, Centro de Investigación Biomédica en Red en Fragilidad y Envejecimiento Saludable (CIBERFES), ISCIII, Barcelona, Spain., Castañeda S; Department of Rheumatology, Hospital Universitario de La Princesa, IIS-Princesa, EPID-Future, Cátedra UAM- Roche, Universidad Autónoma de Madrid, Madrid, 28670, Spain., Balcells S; Dpt. Genetics, Microbiology and Statistics, Facultat de Biologia, IBUB, Universitat de Barcelona, Barcelona, Spain.; Centro de Investigación Biomédica en Red-Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.; Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, Spain., Rabionet R; Dpt. Genetics, Microbiology and Statistics, Facultat de Biologia, IBUB, Universitat de Barcelona, Barcelona, Spain.; Centro de Investigación Biomédica en Red-Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain.; Institut de Recerca Sant Joan de Déu (IRSJD), Esplugues de Llobregat, Spain.
Jazyk: angličtina
Zdroj: Human genomics [Hum Genomics] 2024 Aug 15; Vol. 18 (1), pp. 87. Date of Electronic Publication: 2024 Aug 15.
DOI: 10.1186/s40246-024-00652-2
Abstrakt: Background: Recent studies suggested that genetic variants associated with monogenic bone disorders were involved in the pathogenesis of atypical femoral fractures (AFF). Here, we aim to identify rare genetic variants by whole exome sequencing in genes involved in monogenic rare skeletal diseases in 12 women with AFF and 4 controls without any fracture.
Results: Out of 33 genetic variants identified in women with AFF, eleven (33.3%) were found in genes belonging to the Wnt pathway (LRP5, LRP6, DAAM2, WNT1, and WNT3A). One of them was rated as pathogenic (p.Pro582His in DAAM2), while all others were rated as variants of uncertain significance according to ClinVar and ACMG criteria.
Conclusions: Osteoporosis, rare bone diseases, and AFFs may share the same genes, thus making it even more difficult to identify unique risk factors.
(© 2024. The Author(s).)
Databáze: MEDLINE
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