Musculoskeletal Research Group, Hospital del Mar Research Institute, Centro de Investigación Biomédica en Red en Fragilidad y Envejecimiento Saludable (CIBERFES), ISCIII, Barcelona, Spain.
Dpt. Genetics, Microbiology and Statistics, Facultat de Biologia, IBUB, Universitat de Barcelona, Barcelona, Spain.
Hum Genomics. 2024 Aug 15;18(1):87. doi: 10.1186/s40246-024-00652-2.
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.
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.
Osteoporosis, rare bone diseases, and AFFs may share the same genes, thus making it even more difficult to identify unique risk factors.
最近的研究表明，与单基因骨疾病相关的遗传变异可能参与了非典型股骨骨折（AFF）的发病机制。在这里，我们旨在通过全外显子组测序鉴定 12 名 AFF 女性和 4 名无骨折对照组中涉及单基因罕见骨骼疾病的基因中的罕见遗传变异。
在 AFF 女性中发现的 33 种遗传变异中，有 11 种（33.3%）存在于属于 Wnt 途径的基因中（LRP5、LRP6、DAAM2、WNT1 和 WNT3A）。其中一个被评为致病性（p.Pro582His 在 DAAM2 中），而根据 ClinVar 和 ACMG 标准，其他所有变异均被评为意义不明的变异。
骨质疏松症、罕见骨骼疾病和 AFF 可能具有相同的基因，因此更难以确定独特的危险因素。
