Somatic GATA5 mutations in sporadic tetralogy of Fallot

Huang,Ri-Tai; Xue,Song; Xu,Ying-Jia; Zhou,Min; Yang,Yi-Qing

doi:10.3892/ijmm.2014.1674

Somatic GATA5 mutations in sporadic tetralogy of Fallot

Authors:
- Ri-Tai Huang
- Song Xue
- Ying-Jia Xu
- Min Zhou
- Yi-Qing Yang
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Affiliations: Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P.R. China, Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, P.R. China
Published online on: February 26, 2014 https://doi.org/10.3892/ijmm.2014.1674
Pages: 1227-1235

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Abstract

Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease, with high morbidity and mortality rates. Accumulating evidence has demonstrated that genetic defects play an important role in the pathogenesis of TOF. However, the molecular basis of TOF in the majority of patients remains to be determined. In the present study, sequence analysis of the coding exons and exon-intron boundaries of GATA5, a gene encoding a zinc finger‑containing transcriptional factor crucial for cardiogenesis, was performed on genomic DNA isolated from resected cardiac tissue and matched blood samples of 85 unrelated patients who underwent surgical repair of TOF. Genotyping was performed on the cardiac tissue and matched blood samples from 63 unrelated patients who underwent cardiac valve replacement due to rheumatic heart disease as well as the blood samples obtained from 200 unrelated healthy individuals. The functional effect of the mutations was evaluated by using a luciferase reporter assay system. As a result, the novel heterozygous GATA5 mutations, p.D203E and p.Y208X, were found in the cardiac tissues of two TOF patients, respectively. There were no mutations in the cardiac tissues obtained from 63 patients with rheumatic heart disease nor in the blood samples obtained from the 348 subjects. Functional analysis revealed that the GATA5 mutants were consistently associated with significantly decreased transcriptional activity compared with their wild-type counterpart. Thus, results of this study showed an association of somatic GATA5 mutations with TOF, providing further insight into the underlying molecular mechanism of TOF.

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