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

期刊论文
出版模式：

开放获取
发表日期：

2024年8月15日

查看全文

Natalia Garcia-Giralt,
Diana Ovejero,
Daniel Grinberg,
Xavier Nogues,
Santos Castañeda,
Susanna Balcells,
Raquel Rabionet

摘要

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.