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

D. Woodrow Benson, G. Michael Silberbach, Ann Kavanaugh-McHugh, Carol Cottrill, Yizhong Zhang, Steve Riggs, Octavia Smalls, Mark C. Johnson, Michael S. Watson, J. G. Seidman, Christine E. Seidman, John Plowden, John Dale Kugler

Research output: Contribution to journalArticle

462 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1567-1573
Number of pages7
JournalJournal of Clinical Investigation
Volume104
Issue number11
DOIs
StatePublished - Jan 1 1999

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Atrioventricular Block
Transcription Factors
Tetralogy of Fallot
Mutation
Atrial Heart Septal Defects
Ventricular Heart Septal Defects
Double Outlet Right Ventricle
Ebstein Anomaly
Tricuspid Valve
Congenital Heart Defects
Homeobox Genes
Morphogenesis
Sequence Analysis
Heart Diseases
Phenotype

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Benson, D. W., Silberbach, G. M., Kavanaugh-McHugh, A., Cottrill, C., Zhang, Y., Riggs, S., ... Kugler, J. D. (1999). Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways. Journal of Clinical Investigation, 104(11), 1567-1573. https://doi.org/10.1172/JCI8154

Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways. / Benson, D. Woodrow; Silberbach, G. Michael; Kavanaugh-McHugh, Ann; Cottrill, Carol; Zhang, Yizhong; Riggs, Steve; Smalls, Octavia; Johnson, Mark C.; Watson, Michael S.; Seidman, J. G.; Seidman, Christine E.; Plowden, John; Kugler, John Dale.

In: Journal of Clinical Investigation, Vol. 104, No. 11, 01.01.1999, p. 1567-1573.

Research output: Contribution to journalArticle

Benson, DW, Silberbach, GM, Kavanaugh-McHugh, A, Cottrill, C, Zhang, Y, Riggs, S, Smalls, O, Johnson, MC, Watson, MS, Seidman, JG, Seidman, CE, Plowden, J & Kugler, JD 1999, 'Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways', Journal of Clinical Investigation, vol. 104, no. 11, pp. 1567-1573. https://doi.org/10.1172/JCI8154
Benson DW, Silberbach GM, Kavanaugh-McHugh A, Cottrill C, Zhang Y, Riggs S et al. Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways. Journal of Clinical Investigation. 1999 Jan 1;104(11):1567-1573. https://doi.org/10.1172/JCI8154
Benson, D. Woodrow ; Silberbach, G. Michael ; Kavanaugh-McHugh, Ann ; Cottrill, Carol ; Zhang, Yizhong ; Riggs, Steve ; Smalls, Octavia ; Johnson, Mark C. ; Watson, Michael S. ; Seidman, J. G. ; Seidman, Christine E. ; Plowden, John ; Kugler, John Dale. / Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways. In: Journal of Clinical Investigation. 1999 ; Vol. 104, No. 11. pp. 1567-1573.
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