Novel Mutationsin the Transcriptional Activator Domain of the Human TBX20 in Patients with Atrial Septal Defect

Abstract

Background. The relevance of TBX20 gene in heart development has been demonstrated in many animal models, but there are few works that try to elucidate the effect of TBX20 mutations in human congenital heart diseases. In these studies, all missense mutations associated with atrial septal defect (ASD) were found in the DNA-binding T-box domain, none in the transcriptional activator domain. Methods. We search for TBX20 mutations in a group of patients with ASD or ventricular septal defect (VSD) using the High Resolution Melting (HRM) method and DNA sequencing. Results. We report three missense mutations (Y309D, T370O, and M395R) within the transcriptional activator domain of human TBX20 that were associated with ASD. Conclusions. This is the first association of TBX20 transcriptional activator domain missense mutations with ASD. These findings could have implications for diagnosis, genetic screening, and patient follow-up.

Relationship between TBX20 gene polymorphism and congenital heart disease

“…Previous studies have shown that TBX20 polymorphisms are closely related to the occurrence and development of CHD in children Kwiatkowski et al, 2015;Lin et al, 2015;Monroy-Muñoz et al, 2015), results of this study were in concordance with those of previous studies. TBX20 SNP loci that have been reported thus far include: rs6950175 and rs3999941.…”

“…An in vivo study has also indicated that by using RNAi technology, knock down of TBX20 or expression of TBX20 mutants causes mammalian heart disease . Furthermore, human studies have shown that missense mutations in the TBX20 gene is closely related to the occurrence of congenital heart disease in children (Monroy-Muñoz et al, 2015). However, the role of TBX20 in a Chinese population, especially children with congenital heart disease, needs to be clarified .…”

TBX20 loss-of-function mutation associated with familial dilated cardiomyopathy

“…By whole-exome sequencing of a three-generation family with ASD, Liu et al [44] detected a novel TBX20 mutation (p.D176N) co-segregated with ASD. By genetic analysis of TBX20 in 38 patients with ASD or ventricular septal defect (VSD), Monroy-Muñoz et al [45] discovered three missense mutations (p.Y309D, p.T370P and p.M395R) in three ASD patients, respectively, and found 12 SNPs previously listed in SNP database, including F256L (rs3999941). Besides, TBX20 mutations were also implicated with VSD and/or double outlet right ventricle [23,38].…”

The Ultrasonic Microsurgical Anatomical Comparative Study of the CHD Fetuses and Their Clinical Significance

“…The genetic factors may have important roles in the development of CHD, and TOF and VSD may have similar molecular mechanisms [ 39 ]. But other scholars [ 40 ] have reported that there were some novel mutations in the transcriptional activator domain of the human TBX20 with ASD.…”