染色体微阵列分析技术对智力障碍或全面发育迟缓患儿遗传学病因的诊断价值  

The diagnostic value of chromosome microarray analysis technique in the genetic causes of children with intellectual disability or global developmental delay

作　　者：吴海荣[1] 李琳[1] 马祎楠[1] 刘春莲 裴珮[1] 郑雪飞[1] 王松涛[1] 肖洋[1] 卜定芳[1] 许玉凤[1] 潘虹[1] 戚豫[1] Wu Hairong;Li Lin;Ma Yinan;Liu Chunlian;Pei Pei;Zheng Xuefei;Wang Songtao;Xiao Yang;Bu Dingfang;Xu Yufeng;Pan Hong;Qi Yu(Department of Central Laboratory,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学第一医院实验中心,北京100034

出　　处：《中华医学杂志》2021年第3期224-228,共5页National Medical Journal of China

摘　　要：目的探讨染色体微阵列分析(CMA)技术在表现为发育迟缓、智力障碍、孤独症谱系障碍(ASD)、癫痫和多发性先天性异常(MCA)等患儿中的诊断价值。方法收集2014至2019年在北京大学第一医院收治的1320例发育迟缓/智力障碍,孤独症、伴或不伴癫痫和MCA患儿,提取外周血DNA,用比较基因组杂交(array-CGH)和单核苷酸多态性(SNP-array)方法分析基因拷贝数变异(CNV),总结CMA技术在智力障碍或全面发育迟缓患儿遗传学病因检测的结果。结果1320例患儿中,染色体非整倍体异常10例,单亲二体6例,嵌合体1例。致病性拷贝数变异320例,可能致病性拷贝数变异23例,两者相加检出率为26%(343/1320)。临床意义不明确CNV 107例,占比8.1%(107/1320)。可能良性CNV 25例,占比2%(25/1320)。良性CNV 20例,占比1.5%(20/1320)。发育迟缓/智力障碍合并MCA的患儿检出率为39.8%(130/327)。结论CMA具有分辨率高、覆盖全基因组的优势。可以检出显微镜下可见的染色体异常以及染色体微小缺失和重复,从而对智力障碍或全面发育迟缓患儿进行遗传病因学诊断。Objective To study the value of chromosome microarray analysis(CMA)application in children with developmental delay(DD),intellectual disability(ID),autistic spectrum disorder(ASD)and multiple congenital anomalies(MCA).Methods Genomic DNA was extracted from peripheral blood samples.Array-based comparative genomic hybridization(array-CGH)analysis and single nucleotide polymorphism array(SNP-array)were performed in 1320 children with DD/ID,ASD,with or without epilepsy and MCA who were admitted to Peking University First Hospital from 2014 to 2019.The results of genetic etiology test of CMA in children with mental retardation or global DD was summarized.Results Of 1320 samples,there were 10 cases of aneuploid abnormality,6 cases of uniparental disomy and one case of mosaicism,respectively.Pathogenic copy number variations(CNVs)were found in 320 cases and pathogenic CNVs were detected in 23 cases,with a combined detection rate of 26%(343/1320).CNVs of uncertain clinical significance occurred in 107 cases,accounting for 8.1%(107/1320).There were 25 cases of possible benign CNVs,accounting for 2%(25/1320),while benign CNVs were reported in 20 cases,accounting for 1.5%(20/1320).The detection rate of MCA with DD/ID was 39.8%(130/327).Conclusions CMA has the advantages of high resolution and covering the whole genome.It can detect the chromosomal abnormalities,microdeletions and duplications seen under the microscope,thus the genetic etiology of children with mental retardation or global DD can be diagnosed.

关 键 词：DNA拷贝数异常 染色体微阵列分析 发育迟缓 智力障碍 

分 类 号：R749.94[医药卫生—神经病学与精神病学]