A TBX5 NONSENSE MUTATION IN SIBLINGS WITH DIVERGENT PHENOTYPES ASSOCIATED WITH ISOLATED SEPTAL DEFECTS

Yashvanthi Borkar; Krishnananda Nayak; Ranjan K Shetty; Rajasekhar Moka

doi:10.22159/ajpcr.2017.v10i9.19628

Authors

Yashvanthi Borkar Department of Cell and Molecular Biology, School of Life Sciences, Manipal University, Manipal, Karnataka, India.
Krishnananda Nayak Department of Cardiovascular Technology, School of Allied Health Sciences, Manipal University, Manipal, Karnataka, Ind
Ranjan K Shetty Department of Cardiology,Kasturba Medical College, Manipal University, Manipal, Karnataka, India.
Rajasekhar Moka Department of Cell and Molecular Biology, School of Life Sciences, Manipal University, Manipal, Karnataka, India. http://orcid.org/0000-0002-5578-8806

DOI:

https://doi.org/10.22159/ajpcr.2017.v10i9.19628

Keywords:

T-box gene, TBX5, Septal defect, Gene variant, Transcription factor, DNA sequencing

Abstract

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Â Objective: Heart septal defects (HSD) account for 50% of the congenital heart malformations and are characterized by the hole in the wall of tissue which separates the heart chambers. The known causes of the SD are multifactorial and complex inheritance.

Methods: Isolated 15 subjects with ostium secundum atrial SD (OS-ASD) and one subject with perimembranous ventricular SD (VSD) among 125 clinically diagnosed SD were included in the study. Sanger sequencing was performed for all the exons of TBX5 genes using genomic DNA of these patients.

Results: Sequence variation c.444 G>A substitution, leads to the alteration of tryptophan residue into premature stop codon at codon 148. We observed a divergent phenotype within a family of four, where one sibling and the mother had OS-ASD, another sibling had phenotype of perimembranous VSD, and the father had normal genotype.

Conclusion: We believe that this novel sequence variant in TBX5 gene is one of the factors in the SD and may hold a key determining the role of TBX5 gene in the heart development.

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Author Biographies

Yashvanthi Borkar, Department of Cell and Molecular Biology, School of Life Sciences, Manipal University, Manipal, Karnataka, India.

Dept of Cell and Molecular Biology

Krishnananda Nayak, Department of Cardiovascular Technology, School of Allied Health Sciences, Manipal University, Manipal, Karnataka, Ind

Dept. of Cardiovascular Technology

Ranjan K Shetty, Department of Cardiology,Kasturba Medical College, Manipal University, Manipal, Karnataka, India.

Dept. of Cardiology

Rajasekhar Moka, Department of Cell and Molecular Biology, School of Life Sciences, Manipal University, Manipal, Karnataka, India.

Dept of Cell and Molecular Biology

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