先天性无丙种球蛋白血症μ重链基因突变一例  

Analysis of mutation in heavy chain-ix （pHC） gene in a Chinese patient with congenital agammaglobulinemia

作　　者：张志勇[1] 赵晓东[1] 王墨[1] 张宇[1] 赵耀[1] 杨锡强[1] 

机构地区：[1]重庆医科大学附属儿童医院肾脏免疫科,400014

出　　处：《中华儿科杂志》2010年第4期279-283,共5页Chinese Journal of Pediatrics

基　　金：教育部新世纪优秀人才支持计划资助项目（NCET-05-0774）;重庆市杰出青年基金资助项目（2008BA5040）

摘　　要：目的探讨1例μ重链（μHC）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，1岁10个月，临床诊断先天性无丙种球蛋白血症，BTK基因分析未见突变。采用PCR方法扩增患儿及父母μHC基因组DNA。采用RT-PCR扩增患儿μHCmRNA。PCR产物直接进行双向序列测定。结果患儿生后8个月开始反复出现发热、咳嗽。11个月出现右侧偏瘫，1岁零8个月出现左髋关节和右膝关节疼痛肿胀。脑脊液常规检查示细胞总数18×10^6／L[参考值（0～15）×10^6／L]，白细胞7×10^6／L[参考值（0～15）×10^6／L]，生化示蛋白0．14g／L（参考值0．15～0．45g／L），糖4．68mmol／L（参考值2．44～4．44mmol／L），氯化物116．3mmol／L（参考值120～132mmol／L）。头颅CT平扫未见明显异常。免疫球蛋白IgG181mg／L，IgA22mg／L，IgM28．8mg／L，IgE4．6U／ml。淋巴细胞分类示T淋巴细胞（CD3＋）67％，B淋巴细胞（CD19＋）为0，NK细胞（CD16＋ CD56＋）32％。基因分析患儿为μHC基因的复合杂合突变。一条等位基因在第4外显子剪接位点发生突变（1956G〉A），患儿父亲为此突变基因的携带者；一条等位基因在第1外显子核苷酸插入导致移码突变（170-175insert C，L11 fs 60X），患儿母亲为此突变基因的携带者。第1外显子插入突变为首次报道的突变类型。患儿μHC cDNA经半巢式PCR扩增并测序，发现第4外显子潜在剪接位点活化导致转录产物插入第4内含子136个核苷酸，导致仅合成分泌型μHC蛋白。结论通过临床筛查和基因分析，在我国首次报道μHC基因复合杂合突变（1956 G〉A和170—175insert C）患儿，并且发现1个第1外显子的新的突变位点。Objective Mutation in the heavy chain μ（μHC） gene causes a rare type of autosomal recessive agammaglobulinemia. Here we report the molecular and clinical characterization of a compound heterozygous mutation in the μHC gene in a patient with autosomal recessive agammaglobulinemia firstly from China. Method A one-year and ten-month-old male patient and his parents were enrolled in this study. No mutation was found in BTK gene. The μHC gene of the 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 μHC transcripts. Sequencing was performed directly on the PCR products bidirectionally. Results Since 8 months of age, the patient had had recurrent fever and persistent cough. He suffered an acute right hemiplegia at 11 months of age and swelling and pain of left hip joint and right knee joint at one year and eight months of age. Cerebrospinal fluid routine examination showed that total cell count was 18 ×10^6/L [normal range （0-15） ×10^6/L], leukocyte count 7 ×10^6/L [ （0-15） ×10^6/L] and biochemical examination showed protein 0. 14 g/L（0. 15-0. 45 g/L）, glucose 4.68 mmol/L （2. 4±4. 44 mmol/L） and chloride 116. 3 mmol/L（ 120-132 mmol/L）. Mycobacterium bovis was identified negative by cerebrospinal fluid smear examination. No obvious abnormity was detected on skull CT examination. Hydrothorax examination showed that total cell count was 848 ×10^6/L, leukocyte count 785 ×10^6/L and protein 30. 8 g/L （ 〈 30 g/L）. Poliovirus isolation from stool sample of the patient was negative. The serum immunoglobulin （Ig） profile was IgG 181 mg/L （normal range, 5.09-10. 09 g/L） ; IgM 28.8 mg/dl （400-1260 mg/dl） and IgA 22 mg/dl （310-670 mg/dl） ,IgE 4. 6 U/ml （normal range 〈 150 U/ml）. There were no B-cells but normal percentage of T-cells （67%） and NK cells （32%） were present in the peripheral blood. The patient had a compound heterozygous

关 键 词：丙种球蛋白缺乏血症 免疫缺陷综合征 突变 IGHM基因 

分 类 号：R725.9[医药卫生—儿科]