NOTCH2, ATIC, MRI1, SLC6A13, ATP13A2 Genetic Variations are Associated with Ventricular Septal Defect in the Chinese Tibetan Population Through Whole-Exome Sequencing

Abstract

Background

Ventricular septal defect (VSD) is the most common congenital cardiac abnormality in children and the second most common in adults. This study aimed to explore the potentially causative genes in VSD patients in the Chinese Tibetan population, and to provide a theoretical basis for the genetic mechanism of VSD.

Methods

Peripheral venous blood was collected from 20 VSD subjects, and whole-genome DNA was extracted. High-throughput sequencing was performed on qualified DNA samples using whole-exome sequencing (WES) technology. After filtering, detecting, and annotating qualified data, single nucleotide variations (SNVs) and insertion-deletion (InDel) markers were analyzed, and data processing software such as GATK, SIFT, Polyphen, and MutationTaster were used for comparative evaluation and prediction of pathogenic deleterious variants associated with VSD.

Results

A total of 4793 variant loci, including 4168 SNVs, 557 InDels and 68 unknown loci and 2566 variant genes were obtained from 20 VSD subjects through bioinformatics analysis. According to the screening of the prediction software and database, the occurrence of VSD was predicted to be associated with five inherited pathogenic gene mutations, all of which were missense mutations, including NOTCH2 (c.1396C >A:p.Gln466Lys), ATIC (c.235C >T:p.Arg79Cys), MRI1 (c.629G >A:p.Arg210Gln), SLC6A13 (c.1138G >A:p.Gly380Arg), ATP13A2 (c.1363C >T:p.Arg455Trp).

Conclusion

This study demonstrated that NOTCH2, ATIC, MRI1, SLC6A13, ATP13A2 gene variants were potentially associated with VSD in Chinese Tibetan population.

Keywords:

• ventricular septal defect
• genes
• genetic variation
• whole-exome sequencing

Data Sharing Statement

The datasets used or analyzed during the current study are available from the corresponding author of Tianbo Jin on reasonable request.

Ethical Approval and Consent to Participate

This study fully followed the principles of the Declaration of Helsinki and was approved by the Ethics Committee of Xizang Minzu University (201808). All participants under the age of 18 years of age, parental/legal guardian consent was obtained.

Acknowledgments

We are very grateful to all the volunteers, clinicians and hospital staff who participated in this study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no competing interests.

Additional information

Funding

This work were supported by National Natural Science Fund (81860600), Open Fund for Key Laboratory of Plateau Hypoxia Environment and Life and Health (XZMU-2022M-H06), Scientific research project of Xizang Minzu University (2022MDY011), Natural Science Foundation of Tibet Autonomous Region (XZ2018ZRG-79(Z)), Postgraduate research innovation and practice project of Xizang Minzu University (Y2022099).