Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways

Citation
Dw. Benson et al., Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways, J CLIN INV, 104(11), 1999, pp. 1567-1573
Citations number
34
Categorie Soggetti
Medical Research General Topics
Journal title
JOURNAL OF CLINICAL INVESTIGATION
ISSN journal
00219738 → ACNP
Volume
104
Issue
11
Year of publication
1999
Pages
1567 - 1573
Database
ISI
SICI code
0021-9738(199912)104:11<1567:MITCTF>2.0.ZU;2-O
Abstract
Heterozygous mutations in NKX2.5, a homeobox transcription factor, were rep orted to cause secundum atrial septal defects and result in atrioventricula r (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, idiopa thic AV block, or tetralogy of Fallot. We identified 7 novel mutations by s equence analysis of the NKX2.5-coding region in 26 individuals. Associated phenotypes included AV block, which was the primary manifestation of cardia c disease in nearly a quarter of affected individuals, as well as atrial se ptal defect and ventricular septal defect. Ventricular septal defect was as sociated with tetralogy of Fallot or double-outlet right ventricle in 3 ind ividuals. Ebstein's anomaly and other tricuspid valve abnormalities were al so 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 variou s congenital heart defects suggests that this transcription factor contribu tes to diverse cardiac developmental pathways.