Faculty Collaboration Database

Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways. J Clin Invest 1999 Dec;104(11):1567-73

Date

12/10/1999

Pubmed ID

10587520

Pubmed Central ID

PMC409866

DOI

10.1172/JCI8154

Scopus ID

2-s2.0-0033430230 (requires institutional sign-in at Scopus site)   592 Citations

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.

Author List

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

MESH terms used to index this publication - Major topics in bold

DNA Mutational Analysis
DNA Primers
Echocardiography
Electrocardiography
Female
Heart
Heart Block
Heart Defects, Congenital
Heterozygote
Homeobox Protein Nkx-2.5
Homeodomain Proteins
Humans
Male
Mutation
Pedigree
Phenotype
Transcription Factors
Xenopus Proteins