评估涉及单基因骨病的基因对非典型股骨骨折病因的影响。

IF 3.8 3区医学 Q2 GENETICS & HEREDITY Human Genomics Pub Date : 2024-08-15 DOI:10.1186/s40246-024-00652-2

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

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引用次数: 0

摘要

背景：最近的研究表明，与单基因骨骼疾病相关的基因变异参与了非典型股骨骨折（AFF）的发病机制。在此，我们旨在通过全外显子组测序鉴定 12 名股骨非典型骨折女性患者和 4 名未发生任何骨折的对照者中涉及单基因罕见骨骼疾病的基因的罕见遗传变异：在 AFF 女性患者中发现的 33 个基因变异中，有 11 个（33.3%）是在 Wnt 通路（LRP5、LRP6、DAAM2、WNT1 和 WNT3A）的基因中发现的。根据 ClinVar 和 ACMG 标准，其中一个变异被评为致病变异（DAAM2 中的 p.Pro582His），其他所有变异均被评为意义不确定的变异：结论：骨质疏松症、罕见骨病和 AFF 可能具有相同的基因，因此更难确定独特的风险因素。

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

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.

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来源期刊

Human Genomics GENETICS & HEREDITY-

CiteScore

6.00

自引率

2.20%

发文量

审稿时长

11 weeks

期刊介绍： Human Genomics is a peer-reviewed, open access, online journal that focuses on the application of genomic analysis in all aspects of human health and disease, as well as genomic analysis of drug efficacy and safety, and comparative genomics. Topics covered by the journal include, but are not limited to: pharmacogenomics, genome-wide association studies, genome-wide sequencing, exome sequencing, next-generation deep-sequencing, functional genomics, epigenomics, translational genomics, expression profiling, proteomics, bioinformatics, animal models, statistical genetics, genetic epidemiology, human population genetics and comparative genomics.