1例NHEJ通路缺陷病患儿临床、免疫学特征及基因突变分析

发布时间：2018-05-26 14:58

本文选题：免疫缺陷病 + 非同源末端连接　；参考：《重庆医科大学》2014年硕士论文

【摘要】：目的：探讨1例疑似非同源末端连接（Non-homologous endjoining，NHEJ）通路缺陷病患儿临床特征、免疫表型及基因突变分析，为临床工作者识别和诊断此病提供信息。方法：对2013年在重庆医科大学附属儿童医院收治的1例表现为小头畸形、生长落后、联合免疫缺陷及自身免疫性疾病的2岁女性患儿及患儿父母进行LIG4基因扩增、PCR产物测序分析、TCR-Vβ亚家族克隆谱型分析、T淋巴细胞增殖实验。结果：该患儿具有NHEJ通路缺陷病典型临床表现，免疫表型为TlowBlowNK+，免疫球蛋白水平IgG、IgM正常或增高，IgA明显降低。LIG4基因测序复合杂合突变（c.26CT，T9I；c.833GT，A278L），均被报道过，，患儿父母为携带者。患儿多数TCR-Vβ亚家族表现为单克隆或寡克隆峰， T淋巴细胞增值实验显示其T淋巴细胞增殖障碍。结论：通过临床、免疫学筛查、基因分析等，发现我国首例LIG4基因复合杂合突变的NHEJ通路缺陷病患儿。对辐照敏感、小头畸形、联合免疫缺陷及自身免疫表现的儿童，应考虑NHEJ通路缺陷病可能，并进行基因分析以确诊。
[Abstract]:Objective: to investigate the clinical features, immunophenotype and gene mutation analysis of a child with suspected non-homologous terminal junction joining (NHEJJ) pathway deficiency disease, and to provide information for the identification and diagnosis of the disease. Methods: a case of microcephaly was treated in the Children's Hospital affiliated to Chongqing Medical University in 2013. TCR-V 尾 subfamily clone patterns were analyzed by sequencing of LIG4 gene amplification products in 2 year old female children with combined immune deficiency and autoimmune diseases and their parents were used to analyze T lymphocyte proliferation. Results: the patient had typical clinical manifestations of NHEJ pathway deficiency disease. The immunophenotype was TlowBlowNK, and the immunoglobulin level was normal or increased. The heterozygosity mutation of NHEJ gene sequencing was c. 26CTT 9 Ig c. 833 GTN A278L, all of which had been reported, and their parents were carriers. Most of the TCR-V 尾 subfamilies showed monoclonal or oligoclonal peaks, and T lymphocyte proliferation was found to be impaired by T lymphocyte proliferation assay. Conclusion: through clinical, immunological screening and gene analysis, the first LIG4 gene heterozygous NHEJ pathway deficiency disease was found in China. For children who are sensitive to irradiation, microcephaly, combined immune deficiency and autoimmune manifestation, the possibility of NHEJ pathway deficiency disease should be considered, and gene analysis should be carried out to confirm the diagnosis.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R392

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