BCL11B基因突变致神经系统发育异常一例并文献复习  

A case report of BCL11B mutation induced neurodevelopmental disorder and literature review

作　　者：阎诗 魏于斯 杨秋韵 杨露 曾婷 唐雪梅[1] 赵晓东[1] 安云飞[1] Yan Shi;Wei Yusi;Yang Qiuyun;Yang Lu;Zeng Ting;Tang Xuemei;Zhao Xiaodong;An Yunfei(Department of Rheumatology and Immunology,Children′s Hospital of Chongqing Medical University,Chongqing Key Laboratory of Child Infection and Immunity,Chongqing 400014,China)

机构地区：[1]重庆医科大学附属儿童医院风湿免疫科,儿童感染免疫重庆市重点实验室,400014

出　　处：《中华儿科杂志》2020年第3期223-227,共5页Chinese Journal of Pediatrics

基　　金：国家卫生计生委公益性行业科研专项(201402012);重庆市科学技术委科技计划项目(cstc2018jscx-msybX0005)。

摘　　要：目的探讨BCL11B基因突变致神经系统发育异常患儿的临床、免疫及基因突变特点。方法回顾性分析2018年12月重庆医科大学附属儿童医院风湿免疫科收治的1例BCL11B基因突变致神经系统发育异常患儿的病例资料,分析其临床表现、精细免疫分型、淋巴细胞功能检测及基因突变特点,并以"BCL11B突变""免疫缺陷49型""BCL11B mutation""immunodeficiency 49"为检索词,检索建库至2019年1月中文数据库(中国知网数据库、万方数据库及维普数据库)及PubMed数据库进行文献复习。结果患儿男,3岁11月龄,因发现发育迟缓2年余入院。体格检查发现有特殊面容(眉毛稀疏且细、小下颌、眼距增宽、双眼球习惯性内聚),语言及运动发育落后,余未见明显异常。辅助检查:免疫球蛋白检测基本正常(IgG 12.90 g/L,IgA 1.02 g/L,IgM 1.15 g/L,IgE 532000 U/L),精细免疫分型:T细胞所占比例(0.828)及绝对数(4.415×10-3/L)升高,B细胞所占比例(0.108)相对降低,但其绝对数(0.574×10-3/L)正常。T细胞受体剪切环含量(228)及T、B细胞的增殖功能均正常。基因检测示BCL11B基因杂合突变,第4外显子c.1887_c.1893delCGGCGGG(p.Gly629Glyfs*92)杂合移码突变。检索符合条件的中文文献0篇。英文文献2篇,共有14例因BCL11B基因突变致神经系统发育异常的患儿(信息完整的13例),共发现13个突变位点,包括7个移码突变、2个无义突变、2个错义突变及2个染色体重排,均为杂合突变。所有患儿均语言及运动发育落后,特殊面容,以眼距增宽、眉毛稀疏和小下颌多见,部分患儿有牙釉质缺损、屈光不正及过敏相关疾病,少数患儿合并免疫系统受损,仅1例患儿有多系统受损及严重联合免疫缺陷。结论BCL11B基因突变会导致神经系统和免疫系统发育异常,其免疫功能受损程度轻重不一。本例患儿BCL11B基因突变为未报道的新突变。Objective To analyze the clinical,immunological and genetic features of a child with BCL11B mutation induced neurodevelopmental disorder.Methods The clinical data and genetic test of a child with BCL11B mutation hospitalized in the Department of Rheumatology and Immunology in Children′s Hospital of Chongqing Medical University in December 2018 were extracted and analyzed.The literature was searched with"BCL11B mutation"and"immunodeficiency 49"as key words in Chinese databases and Pubmed until January 2019 was reviewed.Results A male patient aged 3 years and 11 months with facial dysmorphisms and delayed language and motor development was admitted due to neurodevelopmental retardation over two years.Laboratory tests showed normal human immunoglobulin(IgG 12.90 g/L,IgA 1.02 g/L,IgM 1.15 g/L,IgE 532000 U/L),Trec(228)and proliferation of T and B cells.The lymphocyte subsets revealeda reduced percentage of B cells(0.108)but normal absolute numbers(0.574×10-3/L),and an increased percentage(0.828)as well as absolute numbers(4.415×10-3/L)of T cells.A heterozygous BCL11B mutation was detected by sanger sequencing,showing a de novo frameshift mutation c.1887_c.1893delCGGCGGG in exon 4.Two papers were found which were all in English,with total of 14 patients(13 patients with complete information).Thirteen mutations were reposed,including 7 frameshift,2 nonsense,2 missense,and 2 chromosomal rearrangements;Thirteen patients had heterozygous mutations.All patients had delayed language and motor development and facial dysplasia which were mainly hypertelorism,thin eyebrows and small palpebral fissures.Some patients had dental anomalies,ametropia and allergy,and a few were combined with immune impairment,but without overt signs of immunodeficiency.Only one patient had multisystem anomalies and profound immune deficiency.Conclusions BCL11B is essential for development of the nervous and the immune system.In this study,the de novo mutation of BCL11B gene resulted in neurodevelopmental and immunological disorders.

关 键 词：基因 神经系统 突变 

分 类 号：R72[医药卫生—儿科]