The use of high-resolution SNP arrays to detect congenital cardiac defects

Abstract

Objective

Copy number variations (CNVs) detected by high-resolution single nucleotide polymorphism microarrays (SNP arrays) have been associated with congenital heart defects (CHDs). The genetic mechanism underlying the development of CHDs remains unclear.

Methods

High-resolution SNP arrays were used to detect CNVs and traditional chromosomal analyses, respectively, were carried out on 60 and 249 fetuses from gestational 12–37 weeks old, having isolated or complex CHDs that were diagnosed using prenatal ultrasound.

Results

Twenty of the 60 fetuses (33.5%) had abnormalities, of which 23 CNVs (12 pathogenic, five probable pathogenic and six of undetermined significance) were detected by SNP arrays, and two distinct CNVs were present in three of these fetuses. In addition, in 39 patients with isolated congenital heart disease who had normal karyotypes, abnormal CNVs were present in 28.2% (11/39), and in patients with complex coronary artery disease, 19.0% (4/21) had abnormal karyotypes and 42.9% (9/21) had abnormal CNVs. In patients with complex coronary artery disease, 19.0% (4/21) had abnormal karyotypes and 42.9% (9/21) had abnormal CNVs.

Conclusions

In conclusion, genome-wide high-resolution SNP array can improve the diagnostic rate and uncover additional pathogenic CNVs. The submicroscopic deletions and duplications of Online Mendelian Inheritance in Man (OMIM) genes found in this study have haploinsufficient (deletion) or triplosensitive (duplication) traits, which further clarify the etiology and inheritance of CHDs.

Keywords:

• Chromosomal microarray analysis
• congenital heart defects
• prenatal diagnosis
• copy number variation
• single nucleotide polymorphism microarray

Acknowledgements

The authors would like to thank the Clinical Cytogenetics laboratory for helping the collection of data presented here. We are also grateful to the individuals included in this study as well as their families. We would like to express our sincere gratitude to Professor Richard H. Finnell for his invaluable contributions to the refinement of this manuscript.

Author contributions

Huang Linhuan and Xie Yingjun carried out study design; Cai Danlei, He Zhiming, Luo Yanmin, and Kong Shu performed the experiments; Chen Jiayi, Peng Jiayi, Su Chuqi, and Yang Yinghong prepared Tables 1–3. Huang Linhuan and Xie Yingjun wrote the paper. All authors read and approved the final manuscript.

Ethical approval

Ethical approval was obtained for this study from the First Affiliated Hospital of Sun Yat-sen University.

Consent form

Not applicable.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (No. 81671464), Guangdong Municipal Department of Science and Technology, Municipal Schools (Institutes) Jointly Funded Project, China (No. 2023A03J0386), Guangzhou Medical University, First-class Professional Construction Project in 2022-Enhancement of Undergraduates’ Scientific Research and Innovation Ability Project (No. 02-408-2203-2059), and Key R&D Program of Zhejiang Province of China (No. 2021C03030).