GATA4 plays an important role in embryonic heart development, hence the aim of this study was to find the association of GATA4 mutations with CHD among the south Indian CHD patients.
A number of mutations in GATA4 and NKX2.5 have been identified to be causative for a subset of familial congenital heart defects (CHDs) and a small number of sporadic CHDs.
CNVs were studied using two multiplex ligation-dependent probe amplification (MLPA) kits, SALSA P250-B1® (DiGeorge gene region) and SALSA MLPA P311-A1® CHD-related gene regions (GATA4, NKX2-5, TBX5, BMP4, and CRELD1).
Finally, useful information is yet available with regard to genes causing isolated CHDs in individuals who do not have a genetic syndrome (an example is the mutation of NKX2.5 and GATA4 genes causing atrial septal defect).
Furthermore, the mutation abrogated the synergistic transcriptional activation between NR2F2 and GATA4, another core cardiac transcription factor associated with CHD.
Furthermore, the mutation markedly reduced the synergistic activation between HAND2 and GATA4 or NKX2.5, other two cardiac key transcription factors involved in the pathogenesis of CHD.
Furthermore, the mutation reduced the synergistic activation between TBX20 and NKX2.5 as well as GATA4, two other transcriptional factors previously associated with various CHD, encompassing TOF.
Furthermore, the mutation significantly diminished the synergistic activation between MEF2C and GATA4, another cardiac core transcription factor that has been causally linked to CHD.
However, subgroup analysis by types of CHD indicated that there was no significant association between GATA4 354 A>C mutation and the risk of ventricular septal defects.
In centromeric 8p23.1, microduplications including GATA4 can give rise to non-syndromic CHD but the clinical significance of two smaller centromeric microduplications without GATA4 was uncertain due to severe neurological profiles not usually found in 8p23.1 DS.
In humans, non-synonymous GATA4 sequence variants were associated with ECD (2/43), ASD (1/8), and RV hypoplasia in the context of double inlet left ventricle (1/9), forms of CHD that overlapped with abnormalities seen in the mouse model.
MLPA analysis revealed that normalized MLPA signals were all found within the normal range values for all exons in all patients, excluding a major contribution of GATA4 gene CNVs in CHD pathogenesis.
Mutations in GATA4 have been related to human congenital heart diseases (CHDs) in several studies, whereas mutations in GATA6 have only recently been reported in patients with persistent truncus arteriosus.
Mutations in cardiac transcription factor genes, such as GATA-4, NKX2-5 and TBX5 genes, have been associated to the patients with familial and isolated congenital heart disease (CHD).