淋巴增生性疾病相关基因FAS、FASLG、SH2D1A及XIAP变异型和临床表现

发布时间：2019-04-20 08:48

【摘要】：目的：探讨儿童淋巴增生性疾病(LPDs)的相关基因FAS.FASLG.SH2D1A及XIAP变异与临床表现的关系。方法：收集2008-2011年在我院就诊的长期不明原因发热,具有淋巴细胞增生表现的5名患儿,其中2例同时符合噬血细胞综合征(HLH)临床诊断标准,但化疗效果差；采集外周血提取DNA,进行PCR扩增与DNA序列分析获得基因突变信息；同时对其进行回顾性临床特点分析。结果：5例患儿FAS、FASLG、SH2D1A和XIAP基因外显子全部扩增成功并进行直接序列分析。发现4例患儿FAS基因发生突变,包括拼接位点突变1例,4号外显子突变1例,9号外显子突变2例,此外检出7号外显子同义突变5例。FASLG、SH2D1A和XIAP基因未检出突变。结论：1.FAS基因突变临床表现多样化,有部分表现为HLH；2.FAS基因突变临床症状严重程度与突变位点之间有一定关系,但本组例数偏少,尚需进一步研究；3.临床表现为HLH的FAS基因突变者预后差,HLH-2004方案化疗可暂时缓解,停药后易复发,提示造血干细胞移植可能是必要的治疗方法。
[Abstract]:Objective: to investigate the relationship between FAS.FASLG.SH2D1A and XIAP mutations of (LPDs) gene and clinical manifestations in children with lymphoproliferative diseases. Methods: from 2008 to 2011, 5 children with long-term fever of unknown origin and lymphocytic hyperplasia were collected. Two of them met the clinical diagnostic criteria of hemophagocytic syndrome (HLH) at the same time, but the effect of chemotherapy was poor. DNA, was extracted from peripheral blood for PCR amplification and DNA sequence analysis to obtain gene mutation information, and the clinical features were analyzed retrospectively. Results: the exons of FAS,FASLG,SH2D1A and XIAP gene were amplified successfully and analyzed by direct sequence analysis in 5 children. Mutations in FAS gene were found in 4 children, including splicing site mutation in 1 case, exon 4 mutation in 1 case, exon 9 mutation in 2 cases, and synonymous mutation in exon 7 in 5 cases. No mutations were detected in FASLG, SH2D1A and XIAP genes. Conclusion: the clinical manifestations of 1.FAS gene mutation are diversified, some of them show that the severity of clinical symptoms of HLH;2.FAS gene mutation is related to the mutation site, but the number of cases in this group is relatively small, which needs further study. The prognosis of patients with FAS gene mutation of HLH is poor. HLH-2004 chemotherapy can relieve the disease temporarily and relapse easily after drug withdrawal. It is suggested that hematopoietic stem cell transplantation may be a necessary treatment method.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R725.5

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