Identification of potential pathogenic genes for severe aplastic anemia by whole-exome sequencing.
Identification of potential pathogenic genes for severe aplastic anemia by whole-exome sequencing.
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DOI：
10.1002/jcla.24438
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发表时间：
2022-05
影响因子：
2.7
通讯作者：
Shao, Zonghong
中科院分区：
文献类型：
--
作者：
Zhang, Yang;Zhang, Yu;Ge, Hongyu;Li, Nianbin;Liu, Chunyan;Wang, Ting;Fu, Rong;Shao, Zonghong
重型再生障碍性贫血（SAA）是由于CD 8 + T细胞功能亢进导致的严重骨髓衰竭综合征。然而，SAA的遗传背景仍然未知。本研究旨在探讨SAA患者CD 8 + T细胞可能存在的遗传变异。我们对4名SAA患者和7名正常对照的CD 8 + T细胞进行了全外显子组测序（WES）。将SAA中存在而NC中不存在的突变确定为候选基因。然后，我们将它们与来自先前RNA-seq的不同表达基因（DEG）的富集KEGG途径中的基因进行了比较。在分析突变类型后，我们确定了可能的致病基因，并通过RT-PCR对其进行了验证。最后，我们将它们与DisGeNET数据库中的自身免疫性疾病相关基因进行比较，以选择最可能的致病基因。共发现95个候选突变基因，其中4个可能的致病基因被鉴定为PRSS 1、KCNJ 18、PRSS 2和DGKK。RT-PCR结果显示，与NC相比，SAA患者PRSS 1和KCNJ 18 mRNA表达显著增加（p < 0.05），SAA患者PRSS 2表达也增加但无统计学差异，SAA患者DGKK基因RT-PCR检测不到。此外，PRSS 1与DisGeNET数据库中的自身免疫性疾病相关。CD 8 +T细胞中PRSS 1、KCNJ 18、PRSS 2和DGKK基因突变，尤其是PRSS 1基因突变，可能参与SAA的免疫发病机制。通过全外显子组测序和RNA测序，我们发现CD 8 +T细胞中PRSS 1、KCNJ 18、PRSS 2和DGKK的突变，特别是PRSS 1，可能参与SAA的免疫发病机制。
Severe aplastic anemia (SAA) is a syndrome of severe bone marrow failure due to hyperfunction of CD8+ T cells. While, the genetic background of SAA is still unknown. In this study, we tried to explore the possible genetic variants in CD8+ T cells of SAA patients. We performed whole‐exome sequencing (WES) in CD8+ T cells of 4 SAA patients and 7 normal controls. The mutations that existed in SAA but not in NCs were identified as candidate genes. Then, we compared them with genes in the enriched KEGG pathway of differently expressed genes (DEGs) from previous RNA‐seq. After analyzing the types of mutations, we identified possible pathogenic genes and validated them by RT‐PCR. Finally, we compared them with the autoimmune disease‐related genes in DisGeNET database to select the most possible pathogenic genes. We found 95 candidate mutant genes in which, 4 possible pathogenic genes were identified: PRSS1, KCNJ18, PRSS2, and DGKK. RT‐PCR results showed that compared with NCs, PRSS1 and KCNJ18 mRNA expression was significantly increased in SAA patients (p < 0.05), PRSS2 was also increased in SAA patients but without statistical difference, and DGKK gene could not be detected by RT‐PCR in SAA patients. In addition, PRSS1 was associated with autoimmune diseases from the DisGeNET database. The mutations of PRSS1, KCNJ18, PRSS2, and DGKK, especially PRSS1 in CD8+T cells, may be involved in the immune pathogenesis of SAA. By whole‐exome sequencing and RNA sequencing, we found that the mutations of PRSS1, KCNJ18, PRSS2, and DGKK, especially PRSS1 in CD8+T cells, may be involved in the immune pathogenesis of SAA.
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DOI：
10.1056/nejmoa1414799
发表时间：
2015-07-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Yoshizato T;Dumitriu B;Hosokawa K;Makishima H;Yoshida K;Townsley D;Sato-Otsubo A;Sato Y;Liu D;Suzuki H;Wu CO;Shiraishi Y;Clemente MJ;Kataoka K;Shiozawa Y;Okuno Y;Chiba K;Tanaka H;Nagata Y;Katagiri T;Kon A;Sanada M;Scheinberg P;Miyano S;Maciejewski JP;Nakao S;Young NS;Ogawa S
通讯作者：
Ogawa S
影响因子：
14.9
作者：
Piñero J;Bravo À;Queralt-Rosinach N;Gutiérrez-Sacristán A;Deu-Pons J;Centeno E;García-García J;Sanz F;Furlong LI
通讯作者：
Furlong LI
影响因子：
29.4
作者：
Huang, Haojie;Swidnicka-Siergiejko, Agnieszka Katarzyna;Logsdon, Craig D.
通讯作者：
Logsdon, Craig D.
汉族自身免疫性胰腺炎患者 PRSS1 基因新移码突变的鉴定
影响因子：
2.5
作者：
Gao, F.;Li, Y.;Xu, Z.
通讯作者：
Xu, Z.
DOI：
10.3760/cma.j.issn.0578-1426.2019.05.015
发表时间：
2019-05-01
期刊：
Zhonghua nei ke za zhi
影响因子：
--
作者：
Sun, Y Y;Liu, C Y;Shao, Z H
通讯作者：
Shao, Z H