摘要
目的:探讨全基因组、高分辨率染色体微阵列分析(CMA)技术在先天性心脏病(CHD)婴幼儿遗传病因学诊断中的应用价值。方法:回顾性分析2016年1月至2018年12月在广州医科大学附属广州市妇女儿童医疗中心儿科住院并接受CMA检查的130例先天性心脏病婴幼儿的临床资料。患儿均按照美国Affymetrix公司CytoScan HD技术平台的标准操作流程行全基因组CMA检测,结果采用ChAS(chromosome ana-lysis suite染色体分析套件)软件及相关的生物信息学方法分析。根据CHD患儿是否合并心外异常分为孤立型CHD组和综合征型CHD组;根据CHD患儿解剖学特点对2组患儿CHD表型进行分类,分为简单型CHD组和复杂型CHD组。结果:在130例行CMA的CHD婴幼儿中,共在53例患儿中检出60个有临床意义的拷贝数变异(CNVs),总体检出率为40.8%(53/130例),其中32例(24.6%)患儿的致病性CNVs<107 bp。检出染色体微缺失/重复综合征29例(54.7%),其中最常见的为22q11.2微缺失综合征、Williams-Beuren综合征及Wolf-Hirschhorn综合征。孤立型CHD组致病性CNVs检出率为42.8%(30/70例),综合征型CHD组致病性CNVs检出率为38.3%(23/60例),差异无统计学意义(P=0.60)。简单型CHD致病性CNVs检出率为34.4%(20/58例),复杂型CHD致病性CNVs检出率为45.8%(33/72例),差异无统计学意义(P=0.19)。通过基因型与表型分析,发现SUZ12、DGCR6、YWHAE、CRKL、LZTR1、DLG1、ADAP2、TBX6基因是与CHD相关的候选致病基因。结论:CMA在婴幼儿CHD中具有重要的应用价值,推荐CMA作为CHD婴幼儿临床一线遗传学检测技术,无论哪种类型CHD均应接受CMA检测。
Objective To explore the application value of whole genome and high resolution chromosome microarray analysis(CMA)in genetically etiological diagnosis of infants and young children with congenital heart disease(CHD).Methods The clinical data of 130 infants and young children with CHD who were hospitalized and received CMA test at the Department of Pediatrics,Guangzhou Women and Children′s Medical Center,Guangzhou Medical University from January 2016 to December 2018 were retrospectively analyzed.The whole genome CMA test was carried out as per the standard operating procedure of American Affymetrix CytoScan HD platform.The results were analyzed by using chromosome analysis suite(ChAS)software and related bioinformatics.CHD patients were divided into the isolated CHD group and the syndromic CHD group according to whether they had extracardial abnormalities.According to the CHD phenotype features of these 2 groups obtained by anatomical results,patients were divided into the simple CHD group and the complex CHD group.Results Among 130 CHD infants and young children receiving CMA,there were 60 clinically significant copy number variations(CNVs)detected by CMA in 53 patients,with a diagnostic rate of 40.8%(53/130 cases).The pathogenic CNVs of 32 patients(24.6%)were less than 107 bp.There were 29 cases(54.7%)of genetic syndromes related to chromosomal microdeletion or microduplication.22q11.2 microdeletion syndrome,Williams-Beuren syndrome and Wolf-Hirschhorn syndrome were the most common syndromes.The detection rates of pathogenic CNVs between the isolated CHD group[42.8%(30/70 cases)]and the syndromic CHD group[38.3%(23/60 cases)]was not statistically significantly different(P=0.60).The detection rates of pathogenic CNVs between the simple CHD group[34.4%(20/58 cases)]and the complex CHD group[45.8%(33/72 cases)]was not statistically significantly different(P=0.19).By genotypic and phenotypic analysis,genes such as SUZ12,DGCR6,YWHAE,CRKL,LZTR1,DLG1,ADAP2 and TBX6 were identified as potential candidate pathogenic g
作者
陈晨
邓琼
张雯雯
符芳
李茹
崔彦芹
邓力
Chen Chen;Deng Qiong;Zhang Wenwen;Fu Fang;Li Ru;Cui Yanqin;Deng Li(Department of Respiratory,Guangzhou Women and Children′s Medical Center,Guangzhou Medical University,Guangzhou 510623,China;Prenatal Diagnostic Center,Guangzhou Women and Children′s Medical Center,Guangzhou Medical University,Guangzhou 510623,China;Cardiac Intensive Care Unit,Guangzhou Women and Children′s Medical Center,Guangzhou Medical University,Guangzhou 510623,China)
出处
《中华实用儿科临床杂志》
CSCD
北大核心
2020年第20期1577-1582,共6页
Chinese Journal of Applied Clinical Pediatrics
基金
国家自然科学基金(81771594,81671474)
广东省自然科学基金(2016A030311046,2017A030313460)
广东省科技发展专项资金(前沿与关键技术创新方向-重大科技专项)(2017B020226006)。
关键词
先天性心脏病
拷贝数变异
染色体微阵列分析
微缺失/微重复
候选基因
Congenital heart disease
Copy number variation
Chromosome microarray analysis
Microdeletion or Microduplication
Candidate gene
