Application of chromosome microarray analysis in congenital heart disease in infants and young children / 中华实用儿科临床杂志

ABSTRACT

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 10 7 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 genes of CHD. Conclusions:CMA has important application value in CHD in infants and young children.It is recommended that CMA should be used as the first-line genetic detection technology for CHD infants and children.CHD patients of various types should be tested by CMA.