a presentation on GATA 6 Mutation and Ventricular Septal Deffect (VSD) by Shilpa Kommineni, Jennifer Onyemenau, Peace Deborah Tirnom Jock

1. GATA 6 MUTATION AND
VENTRICULAR SEPTAL
DEFECT(VSD)
Shilpa Kommineni
Jennifer Onyemenau
Peace Deborah Tirnom Jock

2. INTRODUCTION
Ventricular septal defect (VSD) is the most prevalent
defect, occurring in nearly 50% of all children with
congenital cardiovascular anomalies, and in 14-16% of
cardiac defects. Congenital Ventricular Septal
Defect(VSD) may be associated with other cardiovascular
deformations, such as atrial septal defect, pulmonary
artery stenosis, or tetralogy of Fallot. The GATA binding
protein 6 is a gene encoding a zinc finger transcription
factor essential for cardiogenesis1. A mutation in the
GATA6 gene is one of the causes of VSD2.
Objective: To determine the association of GATA6
mutation to VSD.

4. METHODS
Approximately 37 articles were reviewed. Articles used were between the range of 2010-
2017. Other articles that date before 2010 were also viewed in order to build a stronger
knowledge on VSD.
• Pubmed
• Google scholar
• Journal of human genetics

5. RESULTS
• A fault in the p.G220S found in GATA6 has been identified in people with VSD and is
associated with ineffective transcription activity3.
• Two novel sequence alterations were noticed in GATA6 that modified the amino acid
residues (A127V and L198V)4.

6. DISCUSSION
• In the normal heart organogenesis, the VSD occurs when an opening is present in the
ventricular septum, due to incomplete splitting of the ventricles. The effects of mutation
of GATA6 shows an important decrease in transcriptional activity5.
• GATA6 is a crucial controller for the transcription of genes needed for cardiac
morphogenesis and ANF encoding6.
• An early finding of GATA6 abnormality in congenital VSD is useful to prevent
congenital heart failure and pulmonary heart failure7.

7. CONCLUSION
Ineffectiveness of the cardiac transcription factor GATA6 sheds light to the molecular
mechanism related to VSD formation and knowledge in the therapy of this defect8.
Current research is mainly concentrating on the relation between GATA6 mutation and
cardiogenesis without giving direct implication on VSD. So our suggestion for the future
research is to find the direct relation between GATA6 mutation and VSD.

8. REFERENCES
1: Zheng GF1, Wei D, Zhao H, Zhou N, Yang YQ, Liu XY. A novel GATA6 mutation associated with congenital ventricular septal defect. Int J Mol
Med. 2012 Jun;29(6):1065-71. doi: 10.3892/ijmm.2012.930.
2: Wang J, Luo XJ, Xin YF, Liu Y, Liu ZM, Wang Q, Li RG, Fang WY, Wang XZ, Yang YQ. Novel GATA6 mutations associated with congenital
ventricular septal defect or tetralogy of fallot. 2012 Nov;31(11):1610-7. doi: 10.1089/dna.2012.1814.
3: Yang YQ, Li L, Wang J, Liu XY, Chen XZ, Zhang W, Wang XZ, Jiang JQ, Liu X, Fang WY. A novel GATA4 loss-of-function mutation associated
with congenital ventricular septal defect. Pediatr Cardiol. 2012 Apr;33(4):539-46. doi: 10.1007/s00246-011-0146-y.
4: Maitra M, Koenig SN, Srivastava D, Garg V. Identification of GATA6 sequence variants in patients with congenital heart defects. Pediatr Res. 2010
Oct;68(4):281-5. doi: 10.1203/00006450-201011001-00549.4:
5: Zheng GF, Wei D, Zhao H, Zhou N, Yang YQ, Liu XY. A novel GATA6 mutation associated with congenital ventricular septal defect. Int J Mol Med.
2012 Jun;29(6):1065-71. doi: 10.3892/ijmm.2012.930.
6: Tucker NR, Mahida S, Ye J, Abraham EJ, Mina JA, Parsons VA, McLellan MA, Shea MA, Hanley A, Benjamin EJ, Milan DJ, Lin H, Ellinor PT.
Gain-of-function mutations in GATA6 lead to atrial fibrillation. Heart Rhythm. 2017 Feb;14(2):284-291. doi: 10.1016/j.hrthm.2016.10.014.
7: Kodo K, Nishizawa T, Furutani M, Arai S, Yamamura E, Jood K, Takahashi T, MatsuokaR, Yamagishi H. GATA6 mutations cause human cardiac
outflow tract defects by disrupting semaphorin-plexin signaling. Current Issuue> vol. 106 no. 33> Kazuki Kodo, 13933–13938, doi:
10.1073/pnas.0904744106
8: Wu J, Kubota J, Hirayama J, Nagai Y, Nishina S, Yokoi T, Asaoka Y, Seo J, Shimizu N, Kajiho H, Watanabe T, Azuma N, Katada T, Nishina H.
2010. p38 Mitogen-activated protein kinase controls a switch between cardiomyocyte and neuronal commitment of murine embryonic stem cells by
activating myocyte enhancer factor 2C-dependent bone morphogenetic protein 2 transcription. Stem Cells Dev. 19, 1723-1734

9. THANK YOU!