Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-15T11:16:57.584Z Has data issue: false hasContentIssue false
  • English
  • Français

A novel variation of GDF3 in Chinese Han children with a broad phenotypic spectrum of non-syndromic CHDs

Published online by Cambridge University Press:  05 November 2014

Jianmin Xiao ,
Guanyang Kang ,
Jing Wang ,
Tengyan Li ,
Jiuhao Chen ,
Jieyin Wang ,
Wei Li  and
Binbin Wang
Jianmin Xiao
Affiliation:
Department of Cardiology, The Dongguan Affiliated Hospital of Medical College of Jinan University, The Fifth People’s Hospital of Dongguan, Guangdong, China
Guanyang Kang
Affiliation:
Department of Cardiology, The Dongguan Affiliated Hospital of Medical College of Jinan University, The Fifth People’s Hospital of Dongguan, Guangdong, China Medical College of Shantou University, Guangdong, China
Jing Wang
Affiliation:
Center for Genetics, National Research Institute for Family Planning, Beijing, China Department of Medical Genetics, School of Basic Medical Sciences, Capital Medical University, BeijingChina
Tengyan Li
Affiliation:
Center for Genetics, National Research Institute for Family Planning, Beijing, China
Jiuhao Chen
Affiliation:
Department of Pediatrics, The Dongguan Affiliated Hospital of Medical College of Jinan University, The Fifth People’s Hospital of Dongguan, Guangdong, China
Jieyin Wang
Affiliation:
Department of Cardiology, The Dongguan Affiliated Hospital of Medical College of Jinan University, The Fifth People’s Hospital of Dongguan, Guangdong, China
Wei Li
Affiliation:
Department of Pediatrics, The Dongguan Affiliated Hospital of Medical College of Jinan University, The Fifth People’s Hospital of Dongguan, Guangdong, China
Binbin Wang*
Affiliation:
Center for Genetics, National Research Institute for Family Planning, Beijing, China
*
Correspondence to: B. Wang, Center for Genetics, National Research Institute for Family Planning, 12, Dahuisi Road, Haidian, Beijing 100081, China. Tel: +86 106 217 6870; Fax:+86 106 217 9086; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

The GDF3 gene plays a fundamental role in embryonic morphogenesis. Recent studies have indicated that GDF3 plays a previously unrecognised role in cardiovascular system development. Non-syndromic CHDs might be a clinically isolated manifestation of GDF3 mutations. The purpose of the present study was to identify potential pathological mutations in the GDF3 gene in Chinese children with non-syndromic CHDs, and to gain insight into the aetiology of non-syndromic CHDs.

Methods

A total of 200 non-syndromic CHDs patients and 202 normal control patients were sampled. There were two exons of the human GDF3 gene amplified using polymerase chain reaction. The polymerase chain reaction products were purified and directly sequenced.

Results

One missense mutation (c.C635T, p.Ser212 Leu, phenotype: isolated muscular ventricular septal defect) was found that has not been reported previously.

Conclusions

To the best of our knowledge, this is the first study to investigate the role of the GDF3 gene in non-syndromic CHDs. Our results expand the spectrum of mutations associated with CHDs and first suggest the potentially disease-related GDF3 gene variant in the pathogenesis of CHDs.

Keywords

CHDsGDF3mutationventricular septal defect
Type
Original Articles
Information
Cardiology in the Young , Volume 25 , Issue 7 , October 2015 , pp. 1263 - 1267
Check for updates
Copyright
© Cambridge University Press 2014 

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.)

Footnotes

†

These two authors equally contributed to this work.

References

1. Hoffman, JI, Kaplan, S. The incidence of congenital heart disease. J Am Coll Cardiol 2002; 39: 1890–1900.Google Scholar
2. Srivastava, D, Olson, EN. A genetic blueprint for cardiac development. Nature 2000; 407: 221–226.CrossRefGoogle ScholarPubMed
3. Bruneau, BG. The developmental genetics of congenital heart disease. Nature 2008; 451: 943–948.CrossRefGoogle ScholarPubMed
4. Brand, T. Heart development: molecular insights into cardiac specification and early morphogenesis. Dev Biol 2003; 258: 1–19.Google Scholar
5. Beddington, RS, Robertson, EJ. Axis development and early asymmetry in mammals. Cell 1999; 96: 195–209.CrossRefGoogle ScholarPubMed
6. Hyatt, BA, Yost, HJ. The left-right coordinator: the role of Vg1 in organizing left-right axis formation. Cell 1998; 93: 37–46.Google Scholar
7. Chen, J-N, Van Eeden, F, Warren, KS, et al. Left-right pattern of cardiac BMP4 may drive asymmetry of the heart in zebrafish. Development 1997; 124: 4373–4382.Google Scholar
8. Hamada, H, Meno, C, Watanabe, D, Saijoh, Y. Establishment of vertebrate left–right asymmetry. Nat Rev Genet 2002; 3: 103–113.Google Scholar
9. Shen, MM. Nodal signaling: developmental roles and regulation. Development 2007; 134: 1023–1034.CrossRefGoogle Scholar
10. Schier, AF, Shen, MM. Nodal signalling in vertebrate development. Nature 2000; 403: 385–389.Google Scholar
11. Caricasole, AA, van Schaik, RH, Zeinstra, LM, et al. Human growth-differentiation factor 3 (hGDF3): developmental regulation in human teratocarcinoma cell lines and expression in primary testicular germ cell tumours. Oncogene 1998; 16: 95–103.Google Scholar
12. McPherron, AC, Lee, S-J. GDF-3 and GDF-9: two new members of the transforming growth factor-beta superfamily containing a novel pattern of cysteines. J Biol Chem 1993; 268: 3444–3449.Google Scholar
13. Lin, SJ, Lerch, TF, Cook, RW, Jardetzky, TS, Woodruff, TK. The structural basis of TGF-β, bone morphogenetic protein, and activin ligand binding. Reproduction 2006; 132: 179–190.Google Scholar
14. Chen, C, Ware, SM, Sato, A, et al. The Vg1-related protein Gdf3 acts in a Nodal signaling pathway in the pre-gastrulation mouse embryo. Development 2006; 133: 319–329.Google Scholar
15. Ye, M, Berry-Wynne, KM, Asai-Coakwell, M, et al. Mutation of the bone morphogenetic protein GDF3 causes ocular and skeletal anomalies. Hum Mol Genet 2010; 19: 287–298.Google Scholar
16. Andersson, O, Bertolino, P, Ibanez, CF. Distinct and cooperative roles of mammalian Vg1 homologs GDF1 and GDF3 during early embryonic development. Dev Biol 2007; 311: 500–511.Google Scholar
17. Arai, A, Yamamoto, K, Toyama, J. Murine cardiac progenitor cells require visceral embryonic endoderm and primitive streak for terminal differentiation. Dev Dyn 1997; 210: 344–353.Google Scholar
18. Wharton, K, Derynck, R. TGFβ family signaling: novel insights in development and disease. Development 2009; 136: 3691–3697.CrossRefGoogle ScholarPubMed
19. Shi, Y, Massagué, J. Mechanisms of TGF-β signaling from cell membrane to the nucleus. Cell 2003; 113: 685–700.Google Scholar
20. Arai, A, Yamamoto, K, Toyama, J. Murine cardiac progenitor cells require visceral embryonic endoderm and primitive streak for terminal differentiation. Dev Dyn 1997; 210: 344–353.Google Scholar
21. Gannon, M, Bader, D. Initiation of cardiac differentiation occurs in the absence of anterior endoderm. Development 1995; 121: 2439–2450.CrossRefGoogle ScholarPubMed
22. Perea-Gomez, A, Rhinn, M, Ang, S. Role of the anterior visceral endoderm in restricting posterior signals in the mouse embryo. Int J Dev Biol 2001; 45: 311–320.Google Scholar
23. Ricci, M, Mohapatra, B, Urbiztondo, A, et al. Differential changes in TGF-β/BMP signaling pathway in the right ventricular myocardium of newborns with hypoplastic left heart syndrome. J Card Fail 2010; 16: 628–634.Google Scholar
24. Ming, JE, Muenke, M. Multiple hits during early embryonic development: digenic diseases and holoprosencephaly. Am J Hum Genet 2002; 71: 1017–1032.CrossRefGoogle ScholarPubMed