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目的探讨1例由11q23染色体CD3E基因突变导致CD3ε缺陷重症联合免疫缺陷病的临床特征及免疫表型。方法收集近期就诊于重庆医科大学附属儿童医院的1例疑诊CD3ε缺陷致重症联合免疫缺陷病患儿外周血标本,提取外周血单个核细胞(PBMC)及核酸,CDR3扫描谱型技术分析T淋巴细胞受体(TCR)多样性,定量PCR检测TCR重排剪切环(TREC)含量,二代测序筛查免疫相关基因,一代测序验证。结果 TCR Vβ亚家族表现为单克隆或寡克隆峰,提示TCR重组受限;定量PCR未检测到TREC含量提示TCR重组及T细胞胸腺输出严重受损;二代测序显示CD3E基因复合杂合突变,一代测序验证证实。结论通过临床及免疫学分析、二代测序筛查及一代测序证实,确诊1例CD3E基因复合杂合突变致CD3ε缺陷重症联合免疫缺陷病,该病例罕见且临床与免疫学表型复杂,临床诊断存在困难,导致漏诊与延迟诊断,患者死亡率高且均为早期死亡,干细胞移植或基因治疗是其唯一的根治手段,因此提高临床工作者对本病的认识对于早期诊断与针对性治疗至关重要。
Objective To investigate the clinical features and immunophenotype of a case of severe combined immunodeficiency disease caused by CD3E mutation of 11q23 chromosome. Methods The peripheral blood mononuclear cells (PBMCs) and nucleic acids were collected from 1 suspected CD3ε-deficient severe combined immunodeficiency disease children who were admitted to Children’s Hospital Affiliated to Chongqing Medical University recently. The T-lymphocytes Cell receptor (TCR) diversity, quantitative PCR TCR rearrangement shear loop (TREC) content, second-generation sequencing screening of immune-related genes, a generation of sequencing validation. Results TCR Vβ subfamilies showed monoclonal or oligoclonal peaks, which suggested that TCR was restricted. The absence of TREC detected by quantitative PCR suggested that TCR recombination and T cell thymus export were severely impaired. Second-generation sequencing showed that the CD3E gene complex heterozygous mutation, Proof of sequencing verified. Conclusions A case of CD3ε-deficient severe combination immunodeficiency syndrome was diagnosed by clinical and immunological analysis, second-generation sequencing screening and one-generation sequencing. One case of CD3E gene combined with heterozygous mutation was diagnosed as CD3ε-deficient severe combined immunodeficiency disease. The clinical and immunological phenotype was rare and clinical diagnosis There are difficulties, leading to missed diagnosis and delayed diagnosis, patients with high mortality and are early death, stem cell transplantation or gene therapy is its only radical means to improve clinicians understanding of the disease for early diagnosis and targeted treatment is related important.