Hostname: page-component-76fb5796d-vvkck Total loading time: 0 Render date: 2024-04-25T14:25:49.941Z Has data issue: false hasContentIssue false
  • English
  • Français

Sequence variations in GATA4 and CITED2 gene among patients with cardiac septation defects from Xinjiang, China

Published online by Cambridge University Press:  08 March 2024

Renati Imam ,
Maimaitiaili Aizezi ,
Fei Yan ,
Tao Zhu  and
Weimin Zhang Open the ORCID record for Weimin Zhang [Opens in a new window]
Renati Imam
Affiliation:
Department of Cardiac Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China
Maimaitiaili Aizezi
Affiliation:
Department of Cardiac Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, China
Fei Yan
Affiliation:
Department of Cardiac Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
Tao Zhu
Affiliation:
Department of Cardiac Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
Weimin Zhang*
Affiliation:
Department of Cardiac Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
*
Corresponding author: W. Zhang; Email: xjourheart@163.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Studies have shown that genetic factors play an important role in CHD’s development. The mutations in GATA4 and CITED2 genes result in the failure of the heart to develop normally, thereby leading to septal defects. The present study investigated the underlying molecular aetiology of patients with cardiac septation defects from Xinjiang. We investigated variants of the GATA4 and CITED2 gene coding regions in 172 patients with cardiac septation defects by sequencing. Healthy controls (n = 200) were included. Three heterozygous variations (p.V380M, p.P394T, and p.P407Q) of the GATA4 gene were identified in three patients. p.V380M was discovered in a patient with atrial septal defect. p.P394T was noted in a patient with atrial septal defect. p.V380M and p.P407Q of the GATA4 gene were detected in one patient with ventricular septal defect. A novel homozygous variation (p. Sl92G) of the CITED2 gene was found in one patient with ventricular septal defect. Other patients and healthy individuals were normal. The limited prevalence of genetic variations observed in individuals with cardiac septal defects from Xinjiang provides evidence in favour of the hypothesis that CHD is a polygenic hereditary disorder. It is plausible that mutations in the GATA4 and CITED2 genes could potentially underlie the occurrence of idiopathic CHD in affected patients.

Keywords

CHDGATA4 geneCITED2 genesingle-nucleotide variants
Type
Original Article
Information
Cardiology in the Young , First View , pp. 1 - 8
Check for updates
Copyright
© The Author(s), 2024. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Hoffman, J. The global burden of congenital heart disease. Cardiovasc J Afr 2013; 24: 141–145.Google Scholar
Shabana, NA, Shahid, SU, Irfan, U. Genetic contribution to congenital heart disease (CHD). Pediatr Cardiol 2020; 4: 12–23.CrossRefGoogle Scholar
Bruneau, BG. The developmental genetics of congenital heart disease. Nature 2008; 451: 943–948.CrossRefGoogle ScholarPubMed
Reamon-Buettner, SM, Borlak, J. GATA4 zinc finger mutations as a molecular rationale for septation defects of the human heart. J Med Genet 2005; 42: e32–e32.Google Scholar
Bamforth, SD, Bragança, J, Eloranta, JJ, et al. Cardiac malformations, adrenal agenesis, neural crest defects and exencephaly in mice lacking Cited2, a new Tfap2 co-activator. Nat Genet 2001; 29: 469–474.Google Scholar
Garg, V, Kathiriya, IS, Barnes, R, et al. GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5. Nature 2003; 424: 443–447.CrossRefGoogle ScholarPubMed
Sperling, S, Grimm, CH, Dunkel, I, et al. Identification and functional analysis of CITED2 mutations in patients with congenital heart defects. Hum Mutat 2005; 26: 575–582.Google Scholar
Molkentin, JD, Lin, Q, Duncan, SA, et al. Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. Genes Dev 1997; 11: 1061–1072.CrossRefGoogle ScholarPubMed
Narita, N, Bielinska, M, Wilson, DB. Wild-type endoderm abrogates the ventral developmental defects associated with GATA-4 deficiency in the mouse. Dev Biol 1997; 189: 270–274.CrossRefGoogle ScholarPubMed
Zhao, L, Xu, JH, Xu, WJ, et al. A novel GATA4 loss-of-function mutation responsible for familial dilated cardiomyopathy. Int J Mol Med 2014; 33: 654–660.CrossRefGoogle ScholarPubMed
Jiang, JQ, Shen, FF, Fang, WY, Liu, X, Yang, YQ. Novel GATA4 mutations in lone atrial fibrillation. Int J Mol Med 2011; 28: 1025–1032.Google Scholar
Yu, Y, Lei, W, Yang, J, et al. Functional mutant GATA4 identification and potential application in preimplantation diagnosis of congenital heart diseases. Gene 2018; 641: 349–354.Google Scholar
Okubo, A, Miyoshi, O, Baba, K, et al. A novel GATA4 mutation completely segregated with atrial septal defect in a large Japanese family. J Med Genet 2004; 41: e97–e97.Google Scholar
Xiang, R, Fan, LL, Huang, H, et al. A novel mutation of GATA4 (K319E) is responsible for familial atrial septal defect and pulmonary valve stenosis. Gene 2014; 534: 320–323.CrossRefGoogle ScholarPubMed
Tang, ZH, Xia, L, Chang, W, et al. Two novel missense mutations of GATA4 gene in Chinese patients with sporadic congenital heart defects. Chin J Med Genet 2006; 23: 134–137.Google ScholarPubMed
Salazar, M, Consoli, F, Villegas, V, et al. Search of somatic GATA4 and NKX2.5 gene mutations in sporadic septal heart defects. Eur J Med Genet 2011; 54: 306–309.CrossRefGoogle ScholarPubMed
Granados-Riveron, JT, Pope, M, Bu'lock, FA, et al. Combined mutation screening of NKX2-5, GATA4, and TBX5 in congenital heart disease: multiple heterozygosity and novel mutations. Congenit Heart Dis 2012; 7: 151–159.Google Scholar
Orjuela Quintero, DC, Núñez, F, Caicedo, V, et al. Mutations in the GATA4 gen in patients with non-syndromic congenital heart disease. Invest Clin 2014; 55: 207–216.Google ScholarPubMed
Bose, D, D., V, Shetty, M, et al. Identification of intronic-splice site mutations in GATA4 gene in Indian patients with congenital heart disease. Mutat Res 2017; 803-805: 26–34.CrossRefGoogle ScholarPubMed
Qian, Y, Xiao, D, Guo, X, et al. Multiple gene variations contributed to congenital heart disease via GATA family transcriptional regulation. J Transl Med 2017; 15: 69.CrossRefGoogle ScholarPubMed
Liu, Y, Li, B, Xu, Y, et al. Mutation screening of Gata4 gene in CTD patients within Chinese han population. Pediatr Cardiol 2017; 38: 506–512.CrossRefGoogle ScholarPubMed
Schluterman, MK, Krysiak, AE, Kathiriya, IS, et al. Screening and biochemical analysis of GATA4 sequence variations identified in patients with congenital heart disease. Am J Med Genet A 2007; 143A: 817–823.Google Scholar
Dinesh, SM, Lingaiah, K, Savitha, MR, et al. GATA4 specific nonsynonymous single-nucleotide polymorphisms in congenital heart disease patients of Mysore, India. Genet Test Mol Biomarkers 2011; 15: 715–720.CrossRefGoogle ScholarPubMed
Kodo, K, Nishizawa, T, Furutani, M, et al. Genetic analysis of essential cardiac transcription factors in 256 patients with non-syndromic congenital heart defects. Circ J 2012; 76: 1703–1711.CrossRefGoogle ScholarPubMed
Yoshida, A, Morisaki, H, Nakaji, M, et al. Genetic mutation analysis in Japanese patients with non-syndromic congenital heart disease. J Hum Genet 2016; 61: 157–162.Google Scholar
Dixit, R, Narasimhan, C, Balekundri, VI, et al. Functionally significant, novel GATA4 variants are frequently associated with tetralogy of Fallot. Hum Mutat 2018; 39: 1957–1972.Google Scholar
Zhang, W, Li, X, Shen, A, et al. GATA4 mutations in 486 Chinese patients with congenital heart disease. Eur J Med Genet 2008; 51: 527–535.CrossRefGoogle ScholarPubMed
Wang, J, Lu, Y, Chen, H, et al. Investigation of somatic NKX2-5, GATA4 and HAND1 mutations in patients with tetralogy of Fallot. Pathology 2011; 43: 322–326.Google Scholar
Peng, T, Wang, L, Zhou, SF, et al. Mutations of the GATA4 and NKX2.5 genes in Chinese pediatric patients with non-familial congenital heart disease. Genetica 2010; 138: 1231–1240.CrossRefGoogle ScholarPubMed
MacDonald, ST, Bamforth, SD, Chen, CM, et al. Epiblastic Cited2 deficiency results in cardiac phenotypic heterogeneity and provides a mechanism for haploinsufficiency. Cardiovasc Res 2008; 79: 448–457.Google Scholar
Chen, CM, Bentham, J, Cosgrove, C, et al. Functional significance of SRJ domain mutations in CITED2. PLoS One 2012; 7: e46256.CrossRefGoogle ScholarPubMed
Li, Q, Pan, H, Guan, L, et al. CITED2 mutation links congenital heart defects to dysregulation of the cardiac gene VEGF and PITX2C expression. Biochem Biophys Res Commun 2012; 423: 895–899.Google Scholar
Xu, M, Wu, X, Li, Y, et al. CITED2 mutation and methylation in children with congenital heart disease. J Biomed Sci 2014; 21: 7.Google Scholar
Liu, Y, Wang, F, Wu, Y, et al. Variations of CITED2 are associated with congenital heart disease (CHD) in Chinese population. PLoS One 2014; 9: e98157.Google Scholar
Liu, S, Su, Z, Tan, S, et al. Functional analyses of a novel CITED2 nonsynonymous mutation in chinese tibetan patients with congenital heart disease. Pediatr Cardiol 2017; 38: 1226–1231.Google Scholar
Li, B, Pu, T, Liu, Y, et al. CITED2 mutations in conserved regions contribute to conotruncal heart defects in Chinese children. DNA Cell Biol 2017; 36: 589–595.Google Scholar
Dianatpour, S, Khatami, M, Heidari, MM, et al. Novel point mutations of CITED2 gene are associated with non-familial congenital heart disease (CHD) in sporadic pediatric patients. Appl Biochem Biotechnol 2020; 190: 896–906.Google Scholar
Yadav, ML, Jain, D, Neelabh, D, et al. A gain-of-function mutation in CITED2 is associated with congenital heart disease. Mutat Res 2021; 822: 111741.Google Scholar