重症监护病房新生儿重症联合免疫缺陷病筛查结果及致病基因突变分析  

Analysis of screening results of neonatal severe combined immunodeficiency disease in intensive care unit and pathogenic gene mutation

作　　者：杨晓 朱丽娜 马宁[1] 李昊[1] 杨茹莱[2] YANG Xiao;ZHU Lina;MA Ning;LI Hao;YANG Rulai(Faculty of Pediatrics,Chinese PLA General Hospital/Institute of Pediatrics,Seventh Medical Center of PLA General Hospital/National Engineering Laboratory of Key Technologies for Birth Defect Prevention and Control,Beijing 100700,China;Department of Genetics and Metabolism,Children′s Hospital,Zhejiang University School of Medicine/National Center for Clinical Medical Research of Child Health and Disease/National Children′s Regional Medical Center,Hangzhou,Zhejiang 310052,China)

机构地区：[1]中国人民解放军总医院儿科医学部/中国人民解放军总医院第七医学中心儿科研究所/出生缺陷防控关键技术国家工程实验室,北京100700 [2]浙江大学医学院附属儿童医院遗传与代谢科/国家儿童健康与疾病临床医学研究中心/国家儿童区域医疗中心,浙江杭州310052

出　　处：《国际检验医学杂志》2024年第8期902-907,共6页International Journal of Laboratory Medicine

基　　金：国家重点研发计划课题(2018YFC1002701)。

摘　　要：目的 探讨在新生儿重症监护病房(NICU)新生儿中开展重症联合免疫缺陷病(SCID)筛查的意义,以及新生儿性别、胎龄、出生体重和感染对干血斑T细胞受体切除环(TREC)拷贝数检测结果的影响。方法 选取2017年11月16日至2020年6月9日在解放军总医院第七医疗中心NICU住院的227例新生儿作为研究对象,分别按性别、胎龄、出生体重和感染情况进行分组,采用多重实时荧光定量PCR的方法检测TREC拷贝数。分析性别、胎龄、出生体重、感染与TREC拷贝数的关系,并对SCID筛查阳性的新生儿进行全外显子测序分析以明确诊断。结果 不同性别NICU新生儿TREC拷贝数差异无统计学意义(P>0.05);极早产儿组、晚期早产儿组TREC拷贝数高于超早产儿组,差异有统计学意义(P<0.05);TREC拷贝数随着出生体重的增加而稍有增加,但是各组TREC拷贝数差异无统计学意义(P>0.05);感染组TREC拷贝数显著高于非感染组(P<0.05)。16例新生儿SCID筛查阳性,均在SCID致病基因ADA上均检测出2个突变,可以确认为ADA-SCID患者。结论 对NICU新生儿进行SCID早期筛查并对筛查阳性新生儿进行全外显子测序可以明确SCID诊断,对提高SCID患儿生存率有重要意义。NICU新生儿性别、胎龄和出生体重与TREC拷贝数的关系需在扩大样本量后进一步探讨。感染性疾病可能导致SCID筛查的假阳性,应该引起重视。Objective To explore the significance of screening for severe combined immunodeficiency disease(SCID)in neonatal intensive care unit(NICU),and the effects of neonatal sex,gestational age,birth weight and infection on the detection results of TREC copy number.Methods A total of 227 newborns hospitalized in the NICU of the Seventh Medical Center of the PLA General Hospital from November 16,2017 to June 9,2020 were enrolled in the study,and divided into groups according to sex,gestational age,birth weight and infection status.Multiple real-time fluorescent quantitative PCR was used to detect the copy number of TREC.The relationship between sex,gestational age,birth weight,infection and TREC copy number was analyzed,and the whole exon sequencing analysis was performed on the newborns with positive results of SCID screening to confirm the diagnosis.Results There was no significant difference in the copy number of TREC between NICU neonates of different genders(P>0.05).The copy number of TREC in the extremely preterm group and late preterm groups was higher than that in the super preterm group,and the difference was statistically significant(P<0.05).The copy number of TREC slightly increased with the increase of birth weight,but there was no significant difference among all groups(P>0.05).The copy number of TREC in infected group was significantly higher than that in non-infected group(P<0.05).All 16 neonates screened to be positive for SCID were confirmed as ADA-SCID patients with 2 mutations detected on the disease-causing gene ADA.Conclusion Early screening of NICU newborns for SCID and whole exon sequencing of positive newborns can confirm the diagnosis of SCID,which is of great significance to improve the survival rate of children with SCID.The relationship between neonatal sex,gestational age,birth weight and the copy number of TREC in NICU needs to be further explore after expanding the sample size.Infectious diseases can lead to false positives in SCID screening and should be taken seriously.

关 键 词：重症联合免疫缺陷病 新生儿 筛查 新生儿重症监护病房 基因突变 

分 类 号：R725.9[医药卫生—儿科] R725.6[医药卫生—临床医学]