1例ITGB2基因突变致白细胞黏附分子缺陷病Ⅰ型患儿临床分子特征分析  

ITGB2 gene mutation-induced leukocyte adhesion molecular defect typeⅠ:clinical and molecular characteristics analysis

作　　者：李黎[1,3,4,5,6] 周丽娜[3,4,5,6] 赵晓东[3,4,5,6] 蒋利萍[3,4,5,6] 张志勇[2,3,4,5,6] LI Li;ZHOU Lina;ZHAO Xiaodong;JIANG Liping;ZHANG Zhiyong(Department of Endocrine Genetic Metabolism,Children’s Hospital of Chongqing Medical University,Chongqing 400014,China;Department of Rheumatology and Immunology,Children’s Hospital of Chongqing Medical University,Chongqing 400014,China;Ministry of Education Key Laboratory of Child Development and Disorders,Chongqing 400014,China;National Clinical Research Center for Child Health and Disorders,Chongqing 400014,China;China International Science and Technology Cooperation Base of Child Development and Critical Disorders,Chongqing 400014,China;Chongqing Key Laboratory of Child Infection and Immunity,Children’s Hospital of Chongqing Medical University,Chongqing 400014,China)

机构地区：[1]重庆医科大学附属儿童医院内分泌遗传代谢科,400014 [2]重庆医科大学附属儿童医院风湿免疫科,400014 [3]重庆医科大学附属儿童医院儿童发育疾病研究教育部重点实验室,400014 [4]重庆医科大学附属儿童医院国家儿童健康与疾病临床医学研究中心,400014 [5]重庆医科大学附属儿童医院儿童发育重大疾病国家国际科技合作基地,400014 [6]重庆医科大学附属儿童医院儿童感染免疫重庆市重点实验室,400014

出　　处：《免疫学杂志》2021年第8期719-725,共7页Immunological Journal

摘　　要：目的探讨1例白细胞黏附分子缺陷病Ⅰ型(LADⅠ)患儿的临床特征、免疫表型及基因突变特征。方法总结2020年3月在重庆医科大学附属儿童医院就诊的1例LADⅠ型患儿临床资料。提取患儿外周血标本,采用流式细胞术进行T、B细胞亚群检测,流式细胞术检测白细胞表面CD18分子,全外显子二代测序及ITGB2基因测序。结果本例患儿新生儿期起病,主要表现为反复呼吸道、皮肤感染、腹泻及白细胞异常升高。T、B细胞亚群分析提示多个T细胞亚群比值及绝对值较正常值上限升高,绝对值升高明显;但B细胞比值较正常值下限有降低,绝对值在正常范围内;中性粒细胞表面CD18分子表达仅0.35%,较正常对照明显降低;ITGB2基因测序检测到2号及7号外显子分别存在重复突变c.49dupC(p.Leu17Profs^(*)40)和错义突变c.850G>A(p.Gly284Ser),前者为新发突变。结论通过临床、免疫学及基因检测分析,确诊1例白细胞黏附分子缺陷病I型综合征患儿,并发现1个ITGB2基因新发突变。综合免疫学指标结果提示可能存在适应性免疫缺陷。Leukocyte adhesion deficiency type-Ⅰ(LAD-Ⅰ),a rare disorder of leukocyte adhesion and migration,is characterized by umbilical complications,granulocytosis,and diverse infections.This study enrolled a female patient who was diagnosed of LAD-Ⅰ7 months ago with an aim of exploring the clinical manifestations and molecular features.The neonatal onset of this patient was mainly manifested by recurrent respiratory tract infection,skin infections,diarrhea and markedly increased leukocyte counts with a predominace of neutrophils.Immunoscope evaluation revealed that the ratio and absolute value of some T cell subpopulations were higher than the upper limit of the normal,and the absolute value increased significantly;but the B cell ratio was lower than the lower limit of the normal value,and the absolute value was within the normal range.The expression of CD18 molecules on the surface of neutrophils was only 0.35%,which was significantly lower than that of normal controls.In this case,there were two sites in ITGB2 gene that formed complex heterozygous mutation:repeated mutation c.49dupC(p.Leu17Profs^(*)40)and missense mutation c.850G>A(p.Gly284Ser)in exons 2 and 7,respectively,while the previous is a novel mutation.Through clinical,immunological and genetic testing and analysis,a case of leukocyte adhesion molecule deficiency type I syndrome has confirmed and a novel mutation in the ITGB2 gene is identified.The results of comprehensive immunological indicators suggest that there may be adaptive immune deficiency.

关 键 词：白细胞黏附分子缺陷病I型 复合杂合基因突变 原发性免疫缺陷病 

分 类 号：R725[医药卫生—儿科]