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.
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.
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.
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.
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).
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.
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.
The current data suggest that haploinsufficiency of NKX2-5 cause Ebstein anomaly and support previous results showing that NKX2-5 mutations cause ASD and AV conduction defect.
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.