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Genetic screening of 104 patients with congenitally malformed hearts revealed a fresh mutation of GATA4 in those with atrial septal defects

Published online by Cambridge University Press:  13 August 2009

Haruka Hamanoue ,
Sri Endah Rahayuningsih ,
Yuya Hirahara ,
Junko Itoh ,
Utako Yokoyama ,
Takeshi Mizuguchi ,
Hirotomo Saitsu ,
Noriko Miyake ,
Fumiki Hirahara  and
Naomichi Matsumoto
Haruka Hamanoue
Affiliation:
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan Department of Obstetrics and Gynecology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
Sri Endah Rahayuningsih
Affiliation:
Department of Pediatrics, Padjadjaran University Medical School, Hasan Sadikin General Hospital, Bandung, Indonesia
Yuya Hirahara
Affiliation:
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
Junko Itoh
Affiliation:
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
Utako Yokoyama
Affiliation:
Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama, Japan
Takeshi Mizuguchi
Affiliation:
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
Hirotomo Saitsu
Affiliation:
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
Noriko Miyake
Affiliation:
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
Fumiki Hirahara
Affiliation:
Department of Obstetrics and Gynecology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
Naomichi Matsumoto*
Affiliation:
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
*
Correspondence to: Naomichi Matsumoto, M.D., Ph.D., Department of Human Genetics, Yokohama City University Graduate School of Medicine, Fukuura 3-9, Kanazawa-ku, Yokohama 236-0004, Japan. Tel: +81-45-787-2604; Fax: +81-45-786-5219; E-mail: naomat@yokohama-cu.ac.jp
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Abstract

We analysed the GATA binding protein 4 gene, or GATA4, along with the NK2 transcription factor related, locus 5 gene, or NKX2.5, to determine their genetic contribution to 104 sporadic patients in Indonesia with congenitally malformed hearts, 76 cases having atrial septal defect and 28 tetralogy of Fallot. We found only 1 novel mutation of GATA4 in those with atrial septal defecst. Analysis of the genetic background of the parents of the patient showed for the first time that a new mutation of GATA4 can cause sporadic atrial septal defects. We failed to discover any other mutations of either the GATA4 or NKX2-5 genes, supporting the marked genetic heterogeneity of human congenital cardiac defects.

Keywords

genetic inheritancenew mutationinteratrial communications
Type
Original Article
Information
Cardiology in the Young , Volume 19 , Issue 5 , October 2009 , pp. 482 - 485
Copyright
Copyright © Cambridge University Press 2009

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References

1. Hoffman, JI, Kaplan, S. The incidence of congenital heart disease. J Am Coll Cardiol 2002; 39: 1890–1900.Google Scholar
2. 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
3. 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.CrossRefGoogle Scholar
4. Sarkozy, A, Conti, E, Neri, C, et al. Spectrum of atrial septal defects associated with mutations of NKX2.5 and GATA4 transcription factors. J Med Genet 2005; 42: e16.CrossRefGoogle ScholarPubMed
5. Hirayama-Yamada, K, Kamisago, M, Akimoto, K, et al. Phenotypes with GATA4 or NKX2.5 mutations in familial atrial septal defect. Am J Med Genet A 2005; 135: 47–52.Google Scholar
6. Tomita-Mitchell, A, Maslen, CL, Morris, CD, Garg, V, Goldmuntz, E. GATA4 sequence variants in patients with congenital heart disease. J Med Genet 2007; 44: 779–783.CrossRefGoogle ScholarPubMed
7. Rajagopal, SK, Ma, Q, Obler, D, et al. Spectrum of heart disease associated with murine and human GATA4 mutation. J Mol Cell Cardiol 2007; 43: 677–685.CrossRefGoogle ScholarPubMed
8. Posch, MG, Perrot, A, Schmitt, K, et al. Mutations in GATA4, NKX2.5, CRELD1, and BMP4 are infrequently found in patients with congenital cardiac septal defects. Am J Med Genet A 2008; 146: 251–253.CrossRefGoogle Scholar
9. Nemer, G, Fadlalah, F, Usta, J, et al. A novel mutation in the GATA4 gene in patients with Tetralogy of Fallot. Hum Mutat 2006; 27: 293–294.CrossRefGoogle ScholarPubMed
10. Akazawa, H, Komuro, I. Cardiac transcription factor Csx/Nkx2-5: Its role in cardiac development and diseases. Pharmacol Ther 2005; 107: 252–268.CrossRefGoogle ScholarPubMed
11. McElhinney, DB, Geiger, E, Blinder, J, Benson, DW, Goldmuntz, E. NKX2.5 mutations in patients with congenital heart disease. J Am Coll Cardiol 2003; 42: 1650–1655.CrossRefGoogle ScholarPubMed
12. Schott, JJ, Benson, DW, Basson, CT, et al. Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science 1998; 281: 108–111.CrossRefGoogle ScholarPubMed
13. Benson, DW, Silberbach, GM, Kavanaugh-McHugh, A, et al. Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways. J Clin Invest 1999; 104: 1567–1573.CrossRefGoogle ScholarPubMed
14. Goldmuntz, E, Geiger, E, Benson, DW. NKX2.5 mutations in patients with tetralogy of fallot. Circulation 2001; 104: 2565–2568.CrossRefGoogle ScholarPubMed
15. Reamon-Buettner, SM, Hecker, H, Spanel-Borowski, K, et al. Novel NKX2-5 mutations in diseased heart tissues of patients with cardiac malformations. Am J Pathol 2004; 164: 2117–2125.CrossRefGoogle ScholarPubMed
16. Watanabe, Y, Benson, DW, Yano, S, et al. Two novel frameshift mutations in NKX2.5 result in novel features including visceral inversus and sinus venosus type ASD. J Med Genet 2002; 39: 807–811.CrossRefGoogle ScholarPubMed
17. Ikeda, Y, Hiroi, Y, Hosoda, T, et al. Novel point mutation in the cardiac transcription factor CSX/NKX2.5 associated with congenital heart disease. Circ J 2002; 66: 561–563.Google Scholar
18. 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
19. 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; 143: 817–823.CrossRefGoogle Scholar
20. Posch, MG, Berger, F, Perrot, A, Ozcelik, C. We need a detailed phenome in the phenomenon of genetics and congenital heart disease. J Med Genet 2008; 45: 320.CrossRefGoogle Scholar
21. Zhu, W, Shiojima, I, Hiroi, Y, et al. Functional analyses of three Csx/Nkx-2.5 mutations that cause human congenital heart disease. J Biol Chem 2000; 275: 35291–35296.CrossRefGoogle ScholarPubMed
22. Basson, CT, Bachinsky, DR, Lin, RC, et al. Mutations in human TBX5 [corrected] cause limb and cardiac malformation in Holt-Oram syndrome. Nat Genet 1997; 15: 30–35.CrossRefGoogle ScholarPubMed
[23. Li, QY, Newbury-Ecob, RA, Terrett, JA, et al. Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. Nat Genet 1997; 15: 21–29.CrossRefGoogle ScholarPubMed