Mutations in multiple members of the evolutionarily conserved cardiac transcription factor network, including GATA4, cause or predispose to ASDII and PFO.
Our previous study indicated that 8 patients from a family with a history of congenital heart disease had simple atrial septal defect (ASD) and carried the same mutation at codon 310 in the GATA4 gene.
The cardiac transcription factor GATA4 has not previously been implicated in a human disorder but a recent paper by Garg et al. provides evidence of mutations in GATA4 that cause atrial septal defects.
We have performed High resolution melting (HRM) mutation scanning of GATA4 coding exons of nonsyndrome 100 patients as a case group including 39 atrial septal defects (ASD), 57 ventricular septal defects (VSD) and four patients with both above defects and 50 healthy individuals as a control group.
Numerous mutations in NKX2-5 gene have been reported in CHD patients, including atrial septal defect, ventricular septal defect (VSD) and tetrology of Fallot.
The findings expand the spectrum of mutations in NKX2-5 linked to ASD and contribute to genetic counseling, clinical interventions, and prenatal prevention of ASD for individuals with genetic susceptibility.
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).
The coding region of GATA4 and NKX2-5 genes was screened by sequencing in another 30 cases including 10 cases of ventricular septal defect (VSD), 10 cases of atrial septal defect (ASD), 8 cases of VSD combined with ASD and 2 cases of atrioventricular septal defects (AVSD).
We screened 39 probands with familial CHD for mutations in NKX2-5 and discovered a novel mutation in one family (2.5%) with ASD and atrioventricular block.
MATERIAL AND METHODS To investigate the genetic variation of NKX2-5 in Chinese patients with sporadic atrial septal defect, we sequenced the full length of the NKX2-5 gene in the participants of the study.
Heterozygous mutations in the CSX/NKX2-5 (NKX2E) gene have been identified to cause atrial septal defect (ASD) and/or atrioventricular (AV) conduction disturbance in some families.
Heterozygous mutation of human CSX/NKX2.5 has been associated with various congenital heart diseases such as atrial septal defect (ASD), ventricular septal defect, tetralogy of Fallot, and tricuspid valve abnormalities, including Ebstein's anomaly.
Congenital atrial septal defect (ASD) and progressive atriventricular block (AVB) are the two most common phenotypes linked to NK2 homeobox 5 (NKX2.5) mutations in animals and humans.
The gene responsible for ASD was mapped to chromosome 5q35 encoding the transcription factor NKX2-5 that plays an important role for the regulation of septation during cardiac morphogenesis.