弥漫性特发性骨骼增生和焦磷酸钙晶体软骨钙化症患者的全外显子组测序。

IF 1 4区 医学 Q4 RHEUMATOLOGY
Acta reumatologica portuguesa Pub Date : 2020-04-01
Bruna Parreira, Ana Rita Couto, Fabiana Rocha, Madalena Sousa, Vanessa Faustino, Deborah Mary Power, Jácome Bruges-Armas
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引用次数: 0

摘要

目的:DISH/CC是一种鲜为人知的表型,以周围和轴向骨髓瘤钙化为特征,经常满足弥漫性特发性骨骼肥厚症(DISH, MIM 106400)的放射学标准,在某些情况下与焦磷酸钙二水合物(CPPD)软骨钙化症(CC)相关。DISH和CC的同时发生提示了一种共同的致病机制。为了确定易感性的遗传变异,我们对四名表现出这种表型的患者进行了全外显子组测序。材料和方法:筛选外显子组数据,以找到可能与DISH/CC表型相关的一个或一组变体。感兴趣的变异随后被Sanger测序证实。在来自亚速尔群岛的65例DISH/CC患者和118例对照组中筛选选定的变异。使用PLINK V1.07进行统计分析。结果:我们在17个基因中发现了21个与矿化直接或间接相关的遗传变异,其中一些被预测在蛋白质水平上有很强的影响。对改变氨基酸的系统发育分析表明,这些氨基酸要么在脊椎动物中高度保守,要么在哺乳动物中保守。在病例对照分析中,PPP2R2D的rs34473884变异与DISH/CC表型显著相关(p=0.028;Or =1.789, 95% ci = 1.060 - 3.021))。结论:目前和以往对DISH/CC家族的研究结果表明,该表型具有多基因基础。PPP2R2D基因可能以一种未知的方式参与了这种表型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Whole exome sequencing of patients with diffuse idiopathic skeletal hyperostosis and calcium pyrophosphate crystal chondrocalcinosis.

Objectives: DISH/CC is a poorly understood phenotype characterised by peripheral and axial enthesopathic calcifications, frequently fulfilling the radiological criteria for Diffuse Idiopathic Skeletal Hyperostosis (DISH, MIM 106400), and in some cases associated with Calcium Pyrophosphate Dihydrate (CPPD) Chondrocalcinosis (CC). The concurrence of DISH and CC suggests a shared pathogenic mechanism. In order to identify genetic variants for susceptibility we performed whole exome sequencing in four patients showing this phenotype.

Materials and methods: Exome data were filtered in order to find a variant or a group of variants that could be associated with the DISH/CC phenotype. Variants of interest were subsequently confirmed by Sanger sequencing. Selected variants were screened in a cohort of 65 DISH/CC patients vs 118 controls from Azores. The statistical analysis was performed using PLINK V1.07.

Results: We identified 21 genetic variants in 17 genes that were directly or indirectly related to mineralization, several are predicted to have a strong effect at a protein level. Phylogenetic analysis of altered amino acids indicates that these are either highly conserved in vertebrates or conserved in mammals. In case-control analyses, variant rs34473884 in PPP2R2D was significantly associated with the DISH/CC phenotype (p=0.028; OR=1.789, 95% CI= 1.060 - 3.021)).

Conclusion: The results of the present and preceding studies with the DISH/CC families suggests that the phenotype has a polygenic basis. The PPP2R2D gene could be involved in this phenotype in an as yet unknown way.

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来源期刊
Acta reumatologica portuguesa
Acta reumatologica portuguesa 医学-风湿病学
自引率
0.00%
发文量
0
审稿时长
>12 weeks
期刊介绍: Acta Reumatólogica Portuguesa is a scientific peer reviewed journal covering all aspects of rheumatic diseases and related to Rheumatology. The journal publishes original articles, reviews, clinical cases, images in rheumatology, letters to the editor and clinical teaching (e.g. guidelines and clinical protocols). Published since 1973, Acta Reumatológica Portuguesa is the official scientific publication of the Portuguese Society of Rheumatology, a non-profit organization that promotes the knowledge and investigation of rheumatic diseases and the development of Rheumatology.
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