Further delineation of familial polycystic ovary syndrome (PCOS) via whole-exome sequencing: PCOS-related rare FBN3 and FN1 gene variants are identified.
Further delineation of familial polycystic ovary syndrome (PCOS) via whole-exome sequencing: PCOS-related rare FBN3 and FN1 gene variants are identified.
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DOI：
10.1111/jog.15187
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发表时间：
2022-05
期刊：
影响因子：
--
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中科院分区：
文献类型：
--
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通过全外显子组测序鉴定家族性PCOS患者中致病性罕见编码孟德尔/高效大小变异体，以阐明PCOS相关通路。招募了20名根据鹿特丹标准诊断为多囊卵巢综合征的妇女及其受影响的亲属。对31例多囊卵巢综合征先证者及其患病亲属的生殖系DNA进行全外显子组测序。通过途径和化学基因组学分析进一步评估全外显子组测序数据。候选变体的切片分析由VarCards进行功能预测，VarSite对候选蛋白质的3D结构产生影响。在三名患者中发现了两种杂合罕见FBN 3错义变异体，在一名来自三个不同PCOS家族的患者中发现了一种FN 1错义变异体。我们在文献中首次发现了三种新的FBN 3和FN 1变体，并与多囊卵巢综合征相关。进一步的功能研究可能会确定这些新发现的PCOS相关变异的因果关系，它们的作用仍有待研究。我们的发现可能会提高我们对受影响的生物学途径的理解，并确定新的药物靶点。
To identify pathogenic rare coding Mendelian/high-effect size variant(s) by whole-exome sequencing in familial PCOS patients to elucidate PCOS related pathways. Twenty women and their affected available relatives diagnosed with polycystic ovary syndrome according to Rotterdam Criteria were recruited. Whole-exome sequencing on germ-line DNA from 31 polycystic ovary syndrome probands and their affected relatives were performed. Whole-exome sequencing data was further evaluated by pathway and chemogenomics analyses. In-slico analysis of candidate variants were done by VarCards for functional predictions and VarSite for impact on 3D structures in the candidate proteins. Two heterozygous rare FBN3 missense variants in three patients, and one FN1 missense variant in one patient from three different PCOS families were identified. We identified three novel FBN3 and FN1 variants for the first time in the literature and linked with polycystic ovary syndrome. Further functional studies may identify causality of these newly discovered PCOS related variants, and their role yet remain to be investigated. Our findings may improve our understanding of the biologic pathways affected and identify new drug targets
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DOI：
10.1016/j.coemr.2020.02.011
发表时间：
2020-06-01
影响因子：
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作者：
Dapas, Matthew;Dunaif, Andrea
通讯作者：
Dunaif, Andrea
影响因子：
6.1
作者：
Fauser, BCJM;Chang, J;Lobo, R
通讯作者：
Lobo, R
影响因子：
5.8
作者：
Dapas, Matthew;Sisk, Ryan;Hayes, M. Geoffrey
通讯作者：
Hayes, M. Geoffrey
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
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影响因子：
4.4
作者：
Carter H;Douville C;Stenson PD;Cooper DN;Karchin R
通讯作者：
Karchin R