Servicio de Medicina Interna, Hospital UM Valdecilla, Universidad de Cantabria, IDIVAL, Avda Valdecilla sn, 39008, Santander, Spain.
Servicio de Genética, Hospital UM Valdecilla, IDIVAL, Santander, Spain.
Osteoporos Int. 2022 Nov;33(11):2445-2448. doi: 10.1007/s00198-022-06494-9. Epub 2022 Jul 15.
We present a family with a rare mutation of the LRP6 gene and for the first time provide evidence for its association with low bone mineral density.
The Wnt pathway plays a critical role in bone homeostasis. Pathogenic variants of the Wnt co-receptor LRP6 have been associated with abnormal skeletal phenotypes or increased risk of cardiovascular events.
Here we report an index premenopausal patient and her family carrying a rare missense LRP6 pathogenic variant (rs141212743; 0.0002 frequency among Europeans). This variant has been previously associated with metabolic syndrome and atherosclerosis, in the presence of normal bone mineral density. However, the LRP6 variant was associated with low bone mineral density in this family, without evidence for association with serum lipid levels or cardiovascular events.
Thus, this novel association shows that LRP6 pathogenic variants may be involved in some cases of early-onset osteoporosis, but the predominant effect, either skeletal or cardiovascular, may vary depending on the genetic background or other acquired factors.
我们介绍了一个携带有 LRP6 基因突变的罕见病例的家庭，这也是首次提供证据表明该基因突变与低骨密度有关。
Wnt 通路在骨骼动态平衡中起着至关重要的作用。Wnt 共受体 LRP6 的致病变体与异常骨骼表型或增加心血管事件风险有关。
我们报告了一名指数绝经前患者及其携带罕见错义 LRP6 致病变体（rs141212743；欧洲人群中的频率为 0.0002）的家族。先前有研究表明，该变体与代谢综合征和动脉粥样硬化有关，但同时骨密度正常。然而，该 LRP6 变体与该家族的低骨密度有关，与血清脂质水平或心血管事件无关。
因此，这种新的关联表明 LRP6 致病变体可能与某些早发性骨质疏松症有关，但主要影响（骨骼或心血管）可能因遗传背景或其他获得性因素而异。
