Estimating the frequency of causal genetic variants in foetuses with congenital heart defects: a Chinese cohort study

Abstract

Background The belief that genetics plays a major role in the pathogenesis of congenital heart defects (CHD) has grown popular among clinicians. Although some studies have focused on the genetic testing of foetuses with CHD in China, the genotype–phenotype relationship has not yet been fully established, and hotspot copy number variations (CNVs) related to CHD in the Chinese population are still unclear. This cohort study aimed to assess the prevalence of chromosomal abnormalities in Chinese foetuses with different types of CHD. Results In a cohort of 200 foetuses, chromosomal abnormalities were detected in 49 (24.5%) after a prenatal chromosome microarray analysis (CMA), including 23 foetuses (11.5%) with aneuploidies and 26 (13.0%) with clinically significant CNVs. The additional diagnostic yield following whole exome sequencing (WES) was 11.5% (6/52). The incidence of total chromosomal abnormality in the non-isolated CHD group (31.8%) was higher than that in the isolated CHD group (20.9%), mainly because the incidence of aneuploidy was significantly increased when CHD was combined with extracardiac structural abnormalities or soft markers. The chromosomal abnormality rate of the complex CHD group was higher than that of the simple CHD group; however, the difference was not statistically significant (31.8% vs. 23.6%, P = 0.398). The most common CNV detected in CHD foetuses was the 22q11.2 deletion, followed by deletions of 5p15.33p15.31, deletions of 15q13.2q13.3, deletions of 11q24.2q25, deletions of 17p13.3p13.2, and duplications of 17q12. Conclusions CMA is the recommended initial examination for cases of CHD in prenatal settings, for both simple heart defects and isolated heart defects. For cases with negative CMA results, the follow-up application of WES will offer a considerable proportion of additional detection of clinical significance.

The incremental yield of prenatal exome sequencing over chromosome microarray for congenital heart abnormalities: A systematic review and meta‐analysis

“…Corresponding authors for 18 of the original 52 papers were emailed for further information where this was incomplete and four of these responded with complete data for inclusion, of which one was excluded as it had less than 20 cases 19–22 . This left 21 studies included in the final meta‐analysis (incorporating 1957 cases) 19–21,23–40 . Of the 21 studies in this paper, 8 were used in the previous analysis by Mone, et al 10 .…”

“…[19][20][21][22] This left 21 studies included in the final metaanalysis (incorporating 1957 cases). [19][20][21][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] Of the 21 studies in this paper, 8 were used in the previous analysis by Mone, et al 10 Table S1 outlines the study characteristics. Supplementary Figure S1 demonstrates the quality assessment.…”

Prenatal ultrasound phenotypic and genetic etiology of the 17q12 microduplication syndrome

“…This study summarizes the reported ultrasound phenotypes of fetuses with the 17q12 microduplication syndrome ( Table 2 ). Lu et al reported that the 17q12 microduplication was associated with congenital heart defects ( 21 ). However, no ultrasound phenotype of congenital heart defects was found in our study.…”