PMID- 10587520
OWN - NLM
STAT- MEDLINE
DCOM- 20000104
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 104
IP  - 11
DP  - 1999 Dec
TI  - Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac
      developmental pathways.
PG  - 1567-73
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.
FAU - Benson, D W
AU  - Benson DW
AD  - Division of Pediatric Cardiology, Medical University of South Carolina,
      Charleston, South Carolina 29425, USA. bensondw@musc.edu
FAU - Silberbach, G M
AU  - Silberbach GM
FAU - Kavanaugh-McHugh, A
AU  - Kavanaugh-McHugh A
FAU - Cottrill, C
AU  - Cottrill C
FAU - Zhang, Y
AU  - Zhang Y
FAU - Riggs, S
AU  - Riggs S
FAU - Smalls, O
AU  - Smalls O
FAU - Johnson, M C
AU  - Johnson MC
FAU - Watson, M S
AU  - Watson MS
FAU - Seidman, J G
AU  - Seidman JG
FAU - Seidman, C E
AU  - Seidman CE
FAU - Plowden, J
AU  - Plowden J
FAU - Kugler, J D
AU  - Kugler JD
LA  - eng
GR  - 1 P50 HL61006-01/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (DNA Primers)
RN  - 0 (Homeobox Protein Nkx-2.5)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (NKX2-5 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Xenopus Proteins)
SB  - AIM
SB  - IM
CIN - J Clin Invest. 1999 Dec;104(11):1483-4. PMID: 10587507
MH  - DNA Mutational Analysis
MH  - DNA Primers
MH  - Echocardiography
MH  - Electrocardiography
MH  - Female
MH  - Heart/*growth & development
MH  - Heart Block/classification/genetics
MH  - Heart Defects, Congenital/diagnostic imaging/*genetics
MH  - Heterozygote
MH  - Homeobox Protein Nkx-2.5
MH  - Homeodomain Proteins/*genetics
MH  - Humans
MH  - Male
MH  - *Mutation
MH  - Pedigree
MH  - Phenotype
MH  - Transcription Factors
MH  - *Xenopus Proteins
PMC - PMC409866
EDAT- 1999/12/10 00:00
MHDA- 1999/12/10 00:01
CRDT- 1999/12/10 00:00
PHST- 1999/12/10 00:00 [pubmed]
PHST- 1999/12/10 00:01 [medline]
PHST- 1999/12/10 00:00 [entrez]
AID - 10.1172/JCI8154 [doi]
PST - ppublish
SO  - J Clin Invest. 1999 Dec;104(11):1567-73. doi: 10.1172/JCI8154.