两例Omenn综合征的基因诊断及发病机制研究  

Analysis of genetic mutations and pathogenesis for two children with Omenn syndrome

作　　者：许永彬[1] 陈玉冰[1] 陈慧珊[1] 曾华松[1] 

机构地区：[1]广州医科大学附属广州市妇女儿童医疗中心风湿免疫科,510623

出　　处：《中华医学遗传学杂志》2016年第1期38-43,共6页Chinese Journal of Medical Genetics

基　　金：广州市科学信息管理局项目（2012J410031）

摘　　要：目的探讨2例Omenn综合征患儿的临床特征和基因突变类型。方法对2例疑似严重联合免疫缺陷（severecombinedimmunodeficiency，SCID）的患儿及其家族成员的RAGl及RAG2基因进行PCR扩增、测序，对其T细胞受体基因TCRⅧ亚家族克隆谱型进行分析。结果两例患儿均有反复感染病史、红皮病皮疹和脱发秃顶等典型的Omenn综合征的临床表现。例1免疫学表型为T—B-NK＋，例2免疫学表型T十B-NK十、IgE和嗜酸性细胞升高。2例患儿均携带RAGl基因的复合杂合突变。例1基因突变位点为c．1328G〉A（P．R443K）；e．2486—2490delGGAAA（p．R829fsX869），二者均为新突变。例2的突变位点为c．1209C〉T（P．R403w）、C．2892delT（P．ASN964LYSfs＊14），其中e．2892delT（P．ASN964LYSfs＊14）为新突变。两例患儿的父母均为突变携带者。在100名正常儿童中未发现相同的突变。两例患儿的绝大多数TCRVp亚家族基因扫描图呈现单克隆或寡克隆峰，TCR邯多态性严重受阻。植物凝集素刺激淋巴细胞增殖极度低下。结论新发现并确认了3种能够引起Omenn综合征的突变。Omenn综合征患儿发病时间早，病情复杂且进展迅速，早期诊断并迅速干预可以降低死亡率。Objective To explore the clinical characteristics and genetic mutations in two children with Omenn syndromes. Methods Peripheral venous blood samples were collected from 2 children suspected with severe combined immunodeficiency （SCID） and their family members. The samples were subjected to RAG1 and RAG2 gene sequencing and TCR Vfl subclone analysis. Results Both patients had recurrent infections, erythroderma rashes and alopecia baldness. One patient has fit with immunophenotype T-B-NK＋, while another was consistent with typical Omenn syndrome combined with T ＋ B-NK ＋ immunophenotype, IgE and eosinophil increase. Both children have carried compound heterozygous mutations of the RAG1 gene. The first patient carried c. 1328 G~ A （p. R443K） and c. 2486- 2490delGGAAA （p. R829fsX869） mutations, both were of de novel type. The second patient has carried c. 1209C〉T （p. R403W） and c. 2892delT （p. ASN964LYSfs ＊ 14）, with c. 2892delT （p. ASN964LYSfs ＊ 14） being a de novel mutation. The parents of both patients were heterozygous carriers. The same mutations were not found in 100 healthy children. Both patients＇ 24 TCR Vβ subfamilies have presented monoclonal or oligoclonal peaks, with TCR Vβ polymorphism being severely disrupted. Conclusion Three novel mutations have been identified in two children with Omenn syndrome, which featured early onset and rapid progression. Early recognition of the disease and prompt treatment may reduce the mortality.

关 键 词：Omenn综合征 TCR VΒ亚家族 RAG1/RAG2基因突变 联合免疫缺陷 

分 类 号：R440[医药卫生—诊断学] R725.9[医药卫生—临床医学]