TY - JOUR
T1 - Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways
AU - Benson, D. Woodrow
AU - Silberbach, G. Michael
AU - Kavanaugh-McHugh, Ann
AU - Cottrill, Carol
AU - Zhang, Yizhong
AU - Riggs, Steve
AU - Smalls, Octavia
AU - Johnson, Mark C.
AU - Watson, Michael S.
AU - Seidman, J. G.
AU - Seidman, Christine E.
AU - Plowden, John
AU - Kugler, John D.
PY - 1999/12
Y1 - 1999/12
N2 - Heterozygous mutations in NKX2.5, a homeobox transcription factor, were reported to cause secundum atrial septal defects and result in atrioventricular (AV) conduction block during postnatal life. To further characterize the role of NKX2.5 in cardiac morphogenesis, we sought additional mutations in groups of probands with cardiac anomalies and first- degree AV block, idiopathic AV block, or tetralogy of Fallot. We identified 7 novel mutations by sequence analysis of the NKX2.5-coding region in 26 individuals. Associated phenotypes included AV block, which was the primary manifestation of cardiac disease in nearly a quarter of affected individuals, as well as atrial septal defect and ventricular septal defect. Ventricular septal defect was associated with tetralogy of Fallot or double-outlet right ventricle in 3 individuals. Ebstein's anomaly and other tricuspid valve abnormalities were also present. Mutations in human NKX2.5 cause a variety of cardiac anomalies and may account for a clinically significant portion of tetralogy of Fallot and idiopathic AV block. The coinheritance of NKX2.5 mutations with various congenital heart defects suggests that this transcription factor contributes to diverse cardiac developmental pathways.
AB - Heterozygous mutations in NKX2.5, a homeobox transcription factor, were reported to cause secundum atrial septal defects and result in atrioventricular (AV) conduction block during postnatal life. To further characterize the role of NKX2.5 in cardiac morphogenesis, we sought additional mutations in groups of probands with cardiac anomalies and first- degree AV block, idiopathic AV block, or tetralogy of Fallot. We identified 7 novel mutations by sequence analysis of the NKX2.5-coding region in 26 individuals. Associated phenotypes included AV block, which was the primary manifestation of cardiac disease in nearly a quarter of affected individuals, as well as atrial septal defect and ventricular septal defect. Ventricular septal defect was associated with tetralogy of Fallot or double-outlet right ventricle in 3 individuals. Ebstein's anomaly and other tricuspid valve abnormalities were also present. Mutations in human NKX2.5 cause a variety of cardiac anomalies and may account for a clinically significant portion of tetralogy of Fallot and idiopathic AV block. The coinheritance of NKX2.5 mutations with various congenital heart defects suggests that this transcription factor contributes to diverse cardiac developmental pathways.
UR - http://www.scopus.com/inward/record.url?scp=0033430230&partnerID=8YFLogxK
U2 - 10.1172/JCI8154
DO - 10.1172/JCI8154
M3 - Article
C2 - 10587520
AN - SCOPUS:0033430230
SN - 0021-9738
VL - 104
SP - 1567
EP - 1573
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 11
ER -