Clinical and mutational analysis of primary immunodeficiency disease caused by mutations in the STAT1 gene

作者全名："Jiang, Xinhui; Chen, Junhao; Xu, Haixia; Chen, Shuangmei; Xie, Cai; Song, Jin; Li, Yanchao; Wu, Shilan; Shao, Xiaoshan; An, Yunfei; Wang, Bi"

作者地址："[Jiang, Xinhui; Chen, Junhao; Xu, Haixia; Chen, Shuangmei; Xie, Cai; Song, Jin; Li, Yanchao; Wu, Shilan; Shao, Xiaoshan] Guiyang Maternal & Child Hlth Care Hosp, Guiyang 550003, Peoples R China; [An, Yunfei] Chongqing Med Univ, Childrens Hosp, Chongqing 400014, Peoples R China; [Wang, Bi] Guizhou Med Univ, Sch Basic Med, Guiyang 550025, Peoples R China"

通信作者："Shao, XS (通讯作者)，Guiyang Maternal & Child Hlth Care Hosp, Guiyang 550003, Peoples R China.; An, YF (通讯作者)，Chongqing Med Univ, Childrens Hosp, Chongqing 400014, Peoples R China.; Wang, B (通讯作者)，Guizhou Med Univ, Sch Basic Med, Guiyang 550025, Peoples R China."

来源：ARCHIVES OF CLINICAL PSYCHIATRY

ESI学科分类：PSYCHIATRY/PSYCHOLOGY

WOS号：WOS:001027655300017

JCR分区：　

影响因子：　

年份：2022

卷号：49

期号：2

开始页：102

结束页：107

文献类型：Article

关键词：STAT1; mutations; primary immunodeficiency disease

摘要："Objective: We analyzed the clinical characteristics of children with primary immunodeficiency disease caused by mutations in the STAT1 gene, and analyzed the structural and protein expression changes of the mutations, and improved the understanding and treatment of children with primary immunodeficiency disease caused by mutations in clinical work. Methods: The medical history, clinical presentation, ancillary tests, and treatment of a child with primary immunodeficiency disease admitted to our hospital were analyzed in detail. Whole-exome high-throughput sequencing of a clear pathogenic gene associated with the immune system was performed for this child. The results of STAT1 gene mutation were analyzed via bioinformatics analysis. The impact of mutations on protein structure was predicted and analyzed by modeling. The expression of pSTAT1 and STAT1 in sick children and normal subjects was measured by flow cytometry. Results: A 7-year-old boy presented with a complaint of ""fever with headache and vomiting for 3+ days"", and was considered to have ""septic meningitis"" and ""bronchopneumonia"", taking into account the child's ancillary investigations and past history of multiple infections. Whole-exome high-throughput sequencing showed two heterozygous mutations in the STAT1 gene: c.274-1G>C and c.739T>C, respectively. Of these, the c.274-1G>C heterozygous mutation led to a splicing mutation in the amino acid; the c.739T>C heterozygous mutation led to a change in amino acid 247 from cysteine to arginine. Sanger sequencing of the sick child's parents revealed that the father had no variation and the mother had heterozygous variation at the locus for the c.274-1G>C mutation, and that the father had heterozygous variation and the mother had no variation at the locus for the c.739T>C mutation. We made a diagnosis of Immunodeficiency 31B (OMM: 613796). In addition, high-level structural analysis of the STAT1 protein revealed that the c.739T>C mutation led to amino acid changes p.C247R that might affect the protein conformation. The expression of pSTAT1 was higher in the XHT group than in the HC group at 0 min of IFN-& alpha; and IFN-& gamma; stimulation, but the difference was not significant. STAT1 phosphorylation increased significantly in the HC group after IFN-& alpha; stimulation, but decreased in the XHT group instead of increasing STAT1 phosphorylation. Increased STAT1 phosphorylation was observed in PBMC cells in both the HC and XHT groups after IFN-& gamma; stimulation. Compared with the HC group, STAT1 phosphorylation increased insignificantly in the XHT group after IFN-& gamma; stimulation. STAT1 expression was significantly lower in the XHT group than in the HC group within unstimulated PBMC cells. Conclusion: Primary immunodeficiency diseases caused by mutations in the STAT1 gene are a relatively rare group of diseases, characterized clinically by recurrent infections, hepatic insufficiency, platelet and leukocytopenia, etc. These diseases are easily missed and misdiagnosed, and we should raise awareness and clinical attention to them."

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