A Tbx5 Nonsense Mutation in Siblings With Divergent Phenotypes Associated With Isolated Septal Defects

Abstract

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.

Analysis of Gene Copy Number Variations in Patients With Cardiac Septal Defects Using Multiplex Ligation-Dependent Probe Amplification

“…However, duplications and deletions were observed in association with the same phenotypes. In various studies [16,17], similar phenotypes have been observed, where they speculated the variable expressions of the TBX5 gene. However, Liu et al [18] revealed no evidence of GATA4 and NKX2.5 CNVs in the fetal CHD of the Chinese population except for the deletion in 22q11.…”