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两名患有早发性骨质疏松症的兄弟中该基因的杂合变异。

Heterozygous variant in gene in two brothers with early onset osteoporosis.

作者信息

Turin Christie G, Joeng Kyu Sang, Kallish Staci, Raper Anna, Asher Stephanie, Campeau Philippe M, Khan Amna N, Al Mukaddam Mona

机构信息

Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd., 4th floor, Philadelphia, PA 19104, USA.

Mckay Orthopaedic Research Laboratory and Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, 3450 Hamilton Walk, Philadelphia, PA 19104, USA.

出版信息

Bone Rep. 2021 Aug 18;15:101118. doi: 10.1016/j.bonr.2021.101118. eCollection 2021 Dec.

DOI:10.1016/j.bonr.2021.101118
PMID:34458510
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8379666/
Abstract

Osteoporosis is a multifactorial disorder characterized by low bone mass and strength, leading to increased risk of fracture. The WNT pathway plays a critical role in bone remodeling by enhancing osteoblastic differentiation, which promotes bone formation, and inhibiting osteoclastic differentiation, decreasing bone resorption. Therefore, genetic alterations of this pathway will lead to impaired bone homeostasis and could contribute to varying response to treatment. We present the case of two brothers with early osteoporosis who were found to have a heterozygous variant of unknown significance in the gene, c.1060_1061delCAinsG (p.H354Afs*39). This finding demonstrates that frameshift variants in may also act in a dominant fashion leading to decreased bone mass.

摘要

骨质疏松症是一种多因素疾病，其特征是骨量和骨强度降低，导致骨折风险增加。WNT信号通路通过增强促进骨形成的成骨细胞分化和抑制导致骨吸收减少的破骨细胞分化，在骨重塑中起关键作用。因此，该信号通路的基因改变将导致骨稳态受损，并可能导致对治疗的不同反应。我们报告了两兄弟患有早期骨质疏松症的病例，他们被发现该基因存在一个意义不明的杂合变异，即c.1060_1061delCAinsG（p.H354Afs*39）。这一发现表明，该基因的移码变异也可能以显性方式起作用，导致骨量减少。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/238f/8379666/bd691b63b353/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/238f/8379666/1590a3c602d4/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/238f/8379666/d9446f664f35/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/238f/8379666/feb159b43b3a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/238f/8379666/3b47185dbb30/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/238f/8379666/bd691b63b353/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/238f/8379666/1590a3c602d4/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/238f/8379666/d9446f664f35/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/238f/8379666/feb159b43b3a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/238f/8379666/3b47185dbb30/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/238f/8379666/bd691b63b353/gr5.jpg

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本文引用的文献

1
An insight into the paradigms of osteoporosis: From genetics to biomechanics.深入了解骨质疏松症的范式：从遗传学到生物力学。
Bone Rep. 2019 Jul 17;11:100216. doi: 10.1016/j.bonr.2019.100216. eCollection 2019 Dec.
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The genetic architecture of osteoporosis and fracture risk.骨质疏松症和骨折风险的遗传结构。
Bone. 2019 Sep;126:2-10. doi: 10.1016/j.bone.2019.04.005. Epub 2019 Apr 10.
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An atlas of genetic influences on osteoporosis in humans and mice.人类和小鼠骨量疏松遗传影响图谱
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Novel mutation G324C in WNT1 mapped in a large Pakistani family with severe recessively inherited Osteogenesis Imperfecta.在一个有严重隐性遗传性成骨不全症的大型巴基斯坦家族中，WNT1 上的新型突变 G324C。
J Biomed Sci. 2018 Nov 17;25(1):82. doi: 10.1186/s12929-018-0481-x.
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Wnt1 is an Lrp5-independent bone-anabolic Wnt ligand.Wnt1 是一种不依赖于 Lrp5 的骨形成性 Wnt 配体。
Sci Transl Med. 2018 Nov 7;10(466). doi: 10.1126/scitranslmed.aau7137.
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Heterozygous WNT1 variant causing a variable bone phenotype.杂合性 WNT1 变异导致可变的骨骼表型。
Am J Med Genet A. 2018 Nov;176(11):2419-2424. doi: 10.1002/ajmg.a.40347. Epub 2018 Sep 24.
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WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta.WNT1 突变与早发性骨质疏松症和骨发育不全。
N Engl J Med. 2013 May 9;368(19):1809-16. doi: 10.1056/NEJMoa1215458.
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Mutations in WNT1 cause different forms of bone fragility.WNT1 基因突变可导致不同形式的骨脆弱症。
Am J Hum Genet. 2013 Apr 4;92(4):565-74. doi: 10.1016/j.ajhg.2013.02.010. Epub 2013 Mar 14.
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Mutations in WNT1 are a cause of osteogenesis imperfecta.WNT1 基因突变是成骨不全症的一个病因。
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WNT signaling in bone homeostasis and disease: from human mutations to treatments.WNT 信号在骨稳态和疾病中的作用：从人类突变到治疗。
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