白介素7受体α基因缺陷导致严重联合免疫缺陷病一例  

A compound heterozygosity mutation in the interleukin-7 receptor-or gene resulted in severe combined innnunodeficiency in a Chinese patient

作　　者：张志勇[1] 赵晓东[1] 王墨[1] 于洁[2] 安云飞[1] 杨锡强[1] 

机构地区：[1]重庆医科大学附属儿童医院P2实验室,400014 [2]重庆医科大学附属儿童医院血液科,400014

出　　处：《中华儿科杂志》2009年第9期691-695,共5页Chinese Journal of Pediatrics

基　　金：基金项目：教育部新世纪优秀人才支持计划（教技函[2006]6号NCET-05-0774）;重庆市杰出青年基金（CSCT,2008BA5040）

摘　　要：目的探讨我国首例白介素7受体α（IL-7Rα）基因缺陷患儿的临床特征和基因突变类型。方法患儿为男性，5月龄，生后15d开始反复出现发热、咳嗽、腹泻，伴卡介苗接种处破溃、流脓和左腋下包块。采用PCR方法扩增患儿及父母IL-7Rα基因组DNA。采用RT—PCR扩增患儿及父母IL-7RαmRNA。PCR产物直接进行双向序列测定。结果患儿的免疫球蛋白IgG6867ms／L，IgA249mg／L，IgM206mg／L，IgE2．3U／ml。淋巴细胞分类T淋巴细胞（CD3＋）0，B淋巴细胞（CD19＋）58％，NK细胞（CD16＋CD56＋）42％。基因分析患儿为IL-7Rα基因的复合杂合突变。在第4内含子剪接位点＋1位发生突变[intron4（＋1）G〉A]，患儿父亲为此突变基因的携带者；第5外显子638位核苷酸发生无义突变（638C〉T，R206X），患儿母亲为此突变基因的携带者。第4内含子剪接位点突变[intron4（＋1）G〉A]为首次报道的突变类型。RT-PCR检测发现患儿IL-7RotmRNA表达明显降低。患儿IL-7RdcDNA经巢式PCR扩增并T-A克隆，测序发现外显子4出现64个核苷酸缺失（496．559del，K158fsl60X）。结论通过临床筛查和基因分析，鉴定出我国首例IL-7RoL基因复合杂合突变[intron4（＋1）G〉A和638C〉T]患儿。Objective Mutation in the interleukin-7 receptor-α （IL-7R α）chain causes a rare type of severe combined immunodeficiency （SCID） with presence of NK cells in the peripheral blood. Here we report the molecular and clinical characterization of a compound heterozygosity mutation in the interleukin-7 receptor-α gene that resulted in SCID in a patient firstly from China. Method A 5 month-old male patient and his parents were enrolled in this study. Since 15 days of age, the patient had had recurrent fever, persistent cough and diarrhea. He was in poor general condition with pyorrhea and ulceration of the BCG scar. His brother died of severe infection at 4 months of age. He was initially diagnosed as SCID according to clinical manifestation and immunological analysis. A panel of SCID candidate genes including IL-2RG, RAG1/RAG2 and IL-TR a of patient and his parents were amplified by polymerase chain reaction （PCR） from genomic DNA. Reverse transcription polymerase chain reaction（RT-PCR） was used to amplify the IL- 7R α transcripts. Sequencing was performed directly on the PCR products forward and reversely. Result The serum immunoglobulin （Ig） profile was IgG 6867 mg/L （normal range, 3050-8870 mg/L） ; IgM 206 mg/L and IgA 249 mg/L,IgE 2. 3 IU/ml （normal range 〈 150 IU/ml）. The patient was treated with IVIG previously. There were no T-cells but increased percentage of B-cells （58%） and NK cells （42%） in the peripheral blood was found. Needle biopsies from enlarged axillary lymph node was identified positive for Mycobacterium boris under microscope and by culture. The patient had a compound heterozygosity mutation in the IL-7 Rct gene ： on one allele, there was a splice-junction mutation in intron 4 （ intron 4 （ ＋ 1 ） G 〉 A ） ,for which his father was a carrier; whereas on the other allele, a nonsense mutation at position 638 in exon 5 with a premature stop codon （638 C 〉 T, R206X） was identified, for which his mother was a carrier. The splice-junction mutation

关 键 词：重症联合免疫缺陷 白细胞介素7受体α亚单位 突变 

分 类 号：R686[医药卫生—骨科学]