Metabolic, fibrotic and splicing pathways are all altered in Emery-Dreifuss muscular dystrophy spectrum patients to differing degrees.
Metabolic, fibrotic and splicing pathways are all altered in Emery-Dreifuss muscular dystrophy spectrum patients to differing degrees.
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DOI：
10.1093/hmg/ddac264
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发表时间：
2023-03-06
影响因子：
3.5
通讯作者：
中科院分区：
文献类型：
--
作者：
Emery-Dreifuss肌营养不良症（EDMD）是一种遗传和临床上可变的疾病。以前试图利用基因表达变化来寻找其病理机制是无效的，所以我们进行了功能途径分析。对来自10名被诊断患有EDMD谱系疾病的患者的细胞进行RNA-Seq，这些患者在7个基因中具有不同的突变。与对照组相比，通路分析显示，在所有患者中，参与纤维化、代谢、生肌信号传导和剪接的多个基因受到影响。剪接变异体分析揭示了几个重要的肌肉基因的肌肉特异性变异的改变。对代谢途径的更深入分析显示，在14名EDMD谱系患者和7名对照组中，糖酵解和氧化代谢减少，线粒体数量减少。有趣的是，基因表达特征将患者分为三个亚组，这些亚组的区别可能与临床表现的差异有关。最后，患者中miRNA变化的差异表达分析同样突出了纤维化、代谢和肌源性信号通路。该途径方法揭示了转录组谱，其既可用作建立EDMD生物标志物组的模板，又可指导对其病理机制的进一步研究。此外，将特定基因变化分离成似乎与临床表现相关的不同组可能会模板化预后生物标志物的发展，尽管这首先需要在具有更多临床信息的更广泛患者中进行测试。
Emery-Dreifuss muscular dystrophy (EDMD) is a genetically and clinically variable disorder. Previous attempts to use gene expression changes to find its pathomechanism were unavailing, so we engaged a functional pathway analysis. RNA-Seq was performed on cells from 10 patients diagnosed with an EDMD spectrum disease with different mutations in seven genes. Upon comparing to controls, the pathway analysis revealed that multiple genes involved in fibrosis, metabolism, myogenic signaling and splicing were affected in all patients. Splice variant analysis revealed alterations of muscle-specific variants for several important muscle genes. Deeper analysis of metabolic pathways revealed a reduction in glycolytic and oxidative metabolism and reduced numbers of mitochondria across a larger set of 14 EDMD spectrum patients and 7 controls. Intriguingly, the gene expression signatures segregated the patients into three subgroups whose distinctions could potentially relate to differences in clinical presentation. Finally, differential expression analysis of miRNAs changing in the patients similarly highlighted fibrosis, metabolism and myogenic signaling pathways. This pathway approach revealed a transcriptome profile that can both be used as a template for establishing a biomarker panel for EDMD and direct further investigation into its pathomechanism. Furthermore, the segregation of specific gene changes into distinct groups that appear to correlate with clinical presentation may template development of prognostic biomarkers, though this will first require their testing in a wider set of patients with more clinical information.
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影响因子：
3.9
作者：
Choi, Byung-Ok;Kang, Sung Hee;Hyun, Young Se;Kanwal, Sumaria;Park, Sun Wha;Koo, Heasoo;Kim, Sang-Beom;Choi, Young-Chul;Yoo, Jeong Hyun;Kim, Jong-Won;Park, Kee Duk;Choi, Kyoung-Gyu;Kim, Song Ja;Zuechner, Stephan;Chung, Ki Wha
通讯作者：
Chung, Ki Wha
影响因子：
16.6
作者：
Czapiewski R;Batrakou DG;de Las Heras JI;Carter RN;Sivakumar A;Sliwinska M;Dixon CR;Webb S;Lattanzi G;Morton NM;Schirmer EC
通讯作者：
Schirmer EC
DOI：
10.1080/19491034.2018.1467722
发表时间：
2018-01-01
期刊：
Nucleus (Austin, Tex.)
影响因子：
--
作者：
Bernasconi P;Carboni N;Ricci G;Siciliano G;Politano L;Maggi L;Mongini T;Vercelli L;Rodolico C;Biagini E;Boriani G;Ruggiero L;Santoro L;Schena E;Prencipe S;Evangelisti C;Pegoraro E;Morandi L;Columbaro M;Lanzuolo C;Sabatelli P;Cavalcante P;Cappelletti C;Bonne G;Muchir A;Lattanzi G
通讯作者：
Lattanzi G
影响因子：
11.2
作者：
Baker, Naomi L.;Morgelin, Matthias;Lamande, Shireen R.
通讯作者：
Lamande, Shireen R.
影响因子：
4
作者：
EMERY, AEH
通讯作者：
EMERY, AEH