摘要
目的Omenn综合征是罕见的常染色体隐性遗传严重联合免疫缺陷病。探讨1例Omenn综合征患儿的临床特征和基因突变类型，以提高临床医师对该病的认识。方法对1例疑诊严重联合免疫缺陷病患儿进行详细的病史采集和归纳，并采用PCR方法扩增患儿、父母及哥哥RAG1／RAG2基因，PCR产物进行双向序列测定，RT—PCR扩增25个T淋巴细胞受体B链V区（TCRV13）亚家族并进行克隆谱型分析，短核苷酸串联重复序列（short tandum repeat，STR）分析除外母源性T细胞植入。结果患儿具有生后早期反复肺炎、顽固性腹泻、红皮病及肝脾淋巴结肿大，抗生素治疗效果差等临床特点；淋巴细胞分类显示有相当数量的CD3^＋细胞（35．3％），CD19^＋细胞明显降低（0．4％）；PHA刺激淋巴细胞增殖极度低下；患儿25个TCRV[3亚家族均为单克隆或寡克隆，提示TCR库多样性严重受限。RAG1基因组DNA测序发现患儿为RAG1基因的纯合缺失突变（2302delT）。患儿父母及哥哥均为RAG1异常基因携带者。患儿STR分析除外母源性T细胞植入可能。结论Omenn综合征是由RAG1／RAG2基因突变引起的严重联合免疫缺陷病，在我国罕见报道，临床表现为生后早期反复感染及红皮病等，RAG1／RAG2基因突变分析可帮助明确诊断及早期免疫重建和遗传咨询。
Objective Omenn syndrome is a rare autosomal recessive hereditary severe combined immunodeficiency. The purpose of this study was to understand clinical characteristics and genetic mutation type of Omenn syndrome and to improve the recognition of Omenn syndrome among pediatric clinicians. Method One suspected case of severe combined immunodeficiency was found to have pneumonia repeatedly, intractable diarrhea, poor antibiotic treatment effect, lymphadenopathy, hepatosplenomegaly and erythroderma. The patient was diagnosed as having Omenn syndrome by RT-PCR, and the expression of RAG1/RAG2 and gene analysis of RAG1/RAG2 were performed. Result The classification of lymphocyte was CD3 ^＋ cells （35.3%）, CD19 ^＋ cells （0.4%）, CD16 ^＋ cells （57.6%）. After stimulation with phytohemagglutinin （ PHA）, lymphocyte proliferation of the child was extremely low. Genetic studies showed RAG1 homozygous deletion mutation （2302 del T）. He had detectable activated T-lymphocytes with low circulating B-lymphocytes and no evidence of maternal T-cell engrafment as indicated by the short tandem repeat （STR） analysis. Conclusion Omenn syndrome is a severe combined immunodeficiency disease caused by mutations in the RAG1/RAG2 gene. The disease has been reported rarely in China. The clinical manifestations of the disease is early postnatal repeated infections and erythroderma. Mutation analysis of RAG1/RAG2 gene may help to confirm the diagnosis and may be useful in early immune reconstitution and genetic counseling.
出处
《中华儿科杂志》
CAS
CSCD
北大核心
2013年第1期64-68,共5页
Chinese Journal of Pediatrics
基金
贵州省科技厅攻关项目（黔科合S字2007-1046）志谢衷心感重庆医科大学附属儿童医院赵晓尔、张忠勇两位老师在本病例基因分析中所做的工作
