Summary

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.

Introduction

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.

Patient and methods

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.

Conclusion

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.

中文翻译：

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LRP6 突变 (Arg360His) 与低骨密度相关，但与白种人家庭中的心血管事件无关

概括

我们提出了一个具有 LRP6 基因罕见突变的家族，并首次提供了其与低骨矿物质密度相关的证据。

介绍

Wnt 通路在骨稳态中起关键作用。Wnt 共受体 LRP6 的致病性变异与异常骨骼表型或心血管事件风险增加有关。

患者和方法

在这里，我们报告了一名指数绝经前患者及其家人携带罕见的错义LRP6致病变异（rs141212743；在欧洲人中的频率为 0.0002）。在骨矿物质密度正常的情况下，这种变体以前与代谢综合征和动脉粥样硬化有关。然而，LRP6变异与该家族的低骨密度相关，没有证据表明与血脂水平或心血管事件相关。

结论

因此，这种新的关联表明LRP6致病性变异可能与某些早发性骨质疏松症病例有关，但主要影响，无论是骨骼还是心血管，可能因遗传背景或其他后天因素而异。