Prenatal diagnosis of chromosomal aberrations in fetuses with conotruncal heart defects by genome-wide high-resolution SNP array

Abstract

Objectives: To explore chromosomal variations, including copy number variations (CNVs), in fetuses with conotruncal heart defect (CTD).

Methods: During a 5-year period, a total of 129 fetuses with ascertained CTDs were investigated for chromosomal abnormalities using quantitative fluorescence PCR (QF-PCR) and chromosomal microarray analysis (CMA). Fetuses were divided into two subgroups: benign group (with normal QF-PCR results and benign CNVs) and nonbenign group [with aneuploidies, nonbenign CNVs [pathogenic CNVs and CNVs of unknown significance (VOUS)]. Data on fetal structural malformations, chromosomal variations, and pregnancy outcomes were collected and compared.

Results: Of the 129 cases, 17 were found to have common aneuploidies. In the remaining 112 cases with normal a QF-PCR result, pathogenic CNVs, CNVs of VOUS, and benign CNVs were identified in 5.3, 5.3, and 4.5%, respectively. Compared with benign group, fetuses in nonbenign group had a significantly higher rate of neurologic defects (13.8 versus 3.0%, p < .05), overall extracardiac anomalies (86.2 versus 45.0%, p < .05), and perinatal death (57.1 versus 18.4%, p < .05), whereas, no significant difference in that of associated cardiovascular anomalies was noted (48.2 versus 46.0%, p = .29). Among the extracardiac anomalies, thymus abnormalities were strongly associated with nonbenign CNVs (33.3 versus 1% of fetuses in benign group, p < .05).

Conclusions: Pathogenic CNVs, in addition to chromosomal aneuploidies, contributed to the pathogenesis of CTD. The presence of associated extracardiac anomalies including thymus abnormalities correlated with a higher probability of nonbenign chromosomal variations, which was associated with an unfavorable outcome.

Keywords:

• Congenital heart disease
• conotruncal defects
• copy number variants
• high-resolution single-nucleotide polymorphism (SNP) array
• prenatal diagnosis

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by the National Scientific Foundation Committee of China (81571687, 81501491), Guangdong Provincial Department of Science and Technology (2017A020214013), and Guangdong Provincial Medical Research Foundation (A2016006).