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

Xiaohui Zhang; Da Zhen; Xuemei Li; Faling Yi; Zhanhao Zhang; Wei Yang; Xuguang Li; Yemeng Sheng; Xiaoli Liu; Tianbo Jin; Yongjun He

doi:10.2147/PGPM.S404438

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

Pharmgenomics Pers Med. 2023 Apr 27:16:389-400. doi: 10.2147/PGPM.S404438. eCollection 2023.

Authors

Xiaohui Zhang^{1

2

3}, Da Zhen⁴, Xuemei Li^{1

2

5}, Faling Yi^{1

2

5}, Zhanhao Zhang^{1

2

5}, Wei Yang^{1

2

6}, Xuguang Li^{1

2

5}, Yemeng Sheng^{1

2

5}, Xiaoli Liu^{1

2

5}, Tianbo Jin^{1

2

5}, Yongjun He^{1

2

5}

Affiliations

¹ Key Laboratory of High Altitude Hypoxia Environment and Life Health, School of Medicine, Xizang Minzu University, Xianyang, People's Republic of China.
² Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, People's Republic of China.
³ Department of Ultrasound, the Affiliated Hospital of Xizang Minzu University, Xianyang, People's Republic of China.
⁴ Department of Medical, Tibet Autonomous Region Maternity and Children's Hospital, Lhasa, People's Republic of China.
⁵ School of Medicine, Xizang Minzu University, Xianyang, People's Republic of China.
⁶ Department of Emergency, the Affiliated Hospital of Xizang Minzu University, Xianyang, People's Republic of China.

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: genes; genetic variation; ventricular septal defect; whole-exome sequencing.

Grants and 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).