Screening and Analysis of Pathogenic Genes in Families with Atrial Septal Defects

Mengyu YAO; Lijing MA; Ruize KONG; Jie LIU; Yu CAO; Lihong JIANG

doi:10.12259/j.issn.2095-610X.S20220327

Volume 43 Issue 3

Mar. 2022

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Article Navigation > Journal of Kunming Medical University > 2022 > 43(3): 7-12

Mengyu YAO, Lijing MA, Ruize KONG, Jie LIU, Yu CAO, Lihong JIANG. Screening and Analysis of Pathogenic Genes in Families with Atrial Septal Defects[J]. Journal of Kunming Medical University, 2022, 43(3): 7-12. doi: 10.12259/j.issn.2095-610X.S20220327

Citation:

Mengyu YAO, Lijing MA, Ruize KONG, Jie LIU, Yu CAO, Lihong JIANG. Screening and Analysis of Pathogenic Genes in Families with Atrial Septal Defects[J]. Journal of Kunming Medical University, 2022, 43(3): 7-12. doi: 10.12259/j.issn.2095-610X.S20220327

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Screening and Analysis of Pathogenic Genes in Families with Atrial Septal Defects

doi: 10.12259/j.issn.2095-610X.S20220327

Mengyu YAO^{1, 2},
Lijing MA³,
Ruize KONG⁴,
Jie LIU⁵,
Yu CAO^{2
,
,},
Lihong JIANG²

1.
The Affiliated Hospital of Kunming University of Science and Technology，Kunming Yunnan 650500
2.
Dep.t of Cardiovascular Surgery
3.
Dept. of Endocrinology
4.
First Department of General Surgery，The First People’s Hospital of Yunnan Province， Kunming Yunnan 650032
5.
Regenerative Medicine Research Center，Kunming Yunnan 650032，China

Received Date: 2022-02-01
Available Online: 2022-02-18
Publish Date: 2022-03-22

Abstract

Abstract

Objective To screen the pathogenic mutations in the four generations of a proband with atrial septal defect, so as to analyze the relationship between genotype and phenotype by whole exon sequencing and Sanger sequencing. Methods Retrospectic analysis of the clinical data on a child with atrial septal defects treated in the Department of Cardiovascular Surgery, the First People’ s Hospital of Yunnan Province was conducted in tandem with genetic tests for the sick child, his younger brother and mother by means of whole-exome sequencing to find out the genetic causes of the family in combination with bioinformatics analysis. Meanwhile, sporadic ASD patients and healthy people were screened for the Caudal Homebox Gene 4 （CDX4） mutation found in the family. Results The cardiac ultrasound results of the sick child and the intraoperative findings conformed with ASD diagnosis. The genetic tests suggested that CDX4 gene c.C233T homozygous mutation occurred to the child, his mother carries heterozygous mutation of the gene and his younger brother homozygous mutation of it. Codon 233 of exon 1 of CDX4 gene mutated from C to T （c.C233T）, leading to conversion of amino acid 78 from proline to leucine （p.P78L）. Multi-species comparison showed that the locus was highly conserved. The three software programs PROVEAN, Mutation Taster and Mutation Assessor suggested that the mutation was harmful. Of the 198 patients with sporadic atrial septal defects, 5 suffered this gene mutation, but that was not found in the 265 healthy people. According to the Fischer’s Exact Test, CDX4 gene c.C233T homozygous mutation was associated with congenital heart diseases （P = 0.014）. Conclusion CDX4 gene c.C233T （p.P78L） homozygous mutation is the highly likely the pathogenic mutation of the family.
- Atrial Septal Defect,
- Whole exon sequencing,
- CDX4,
- Gene mutation

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References(27)

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