新发BTK基因缺失突变1例并文献复习

New BTK gene deletion mutation:a case report and literature review

目的探讨1例BTK基因大片段缺失导致X-连锁无丙种球蛋白血症患儿的临床表现、检验及基因特点。方法对2016年8月山东第一医科大学附属省立医院收治的1例X-连锁无丙种球蛋白血症患儿的临床表现、检验检查、基因特点进行分析,并在万方、中国知网(CNKI)、PubMed数据库进行文献检索并文献复习。结果患儿,男,7岁7个月,自3岁起反复细菌感染病史。外周血免疫功能提示,CD19+0.06%,IgG<1.42 g/L,IgA<0.23 g/L,IgM 0.44 g/L,免疫功能明显降低;胸部CT提示支气管扩张、支气管肺炎表现。基因检测报告提示,患儿BTK基因第2~5号外显子缺失,患儿母亲相应位点疑似杂合缺失。因2~5号外显子整体缺失突变导致的X-连锁无丙种球蛋白血症在Human Gene Mutation Database(HGMD)专业数据库中尚无报道。随访5年,患儿每1~2个月应用7.5~10 g人免疫球蛋白,未再出现反复细菌性感染,复查胸部CT仍有轻度支气管扩张。患儿母亲再次怀孕后经羊水穿刺行基因检测,未发现胎儿BTK基因异常,患儿弟弟出生后免疫功能正常。结论对反复细菌性感染、支气管扩张患儿需常规进行免疫功能筛查,存在异常者需进行基因检测明确诊断,对于确诊XLA的患儿需规律行静脉输注丙种球蛋白替代治疗。母亲再次怀孕时需进行羊水BTK基因检测。

Objective To investigate the clinical manifestations,laboratory examinations and gene characteristics of a child with X-linked agammaglobulinemia(XLA)caused by a new BTK gene deletion.Methods The clinical manifestations,laboratory examinations and genetic characteristics of a child with XLA admitted to Shandong Provincial Hospital Affiliated to Shandong First Medical University in August 2016 were analyzed,and relevant literature was reviewed in Wanfang,CNKI and PubMed databases.Results The child,male,7 years and 7 months old,had a history of repeated bacterial infection since the age of 3.Peripheral blood immune function showed CD19+0.06%,IgG<1.42 g/L,IgA<0.23 g/L,IgM 0.44 g/L,with significantly reduced immune function.Chest CT showed bronchiectasis and bronchopneumonia.Gene test report suggested deletion of exon 2-5 of BTK gene,and the mother of the child was suspect of heterozygous deletion.There are no reports in the Human Gene Mutation Database(HGMD)of X-linked gammaglobulinemia due to a deletion mutation in exons 2-5.In 5 years of follow-up,the patient received 7.5-10 g of human immunoglobulin every 1-2 months,and no repeated bacterial infection occurred.Chest CT showed mild bronchiectasis.The childs mother was pregnant again and genetic testing by amniocentesis revealed no fetal BTK gene abnormality,and the childs brother was born with normal immune function.Conclusion Children with recurrent bacterial infections and bronchiectasis should be routinely screened for immune function,and those with abnormalities should be genetically tested for a definitive diagnosis.Children with confirmed XLA should be treated regularly with intravenous gamma globulin replacement therapy.Genetic testing of amniotic fluid for BTK is required if the mother becomes pregnant again.