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Science 3 July 1998:
Vol. 281. no. 5373, pp. 108 - 111
DOI: 10.1126/science.281.5373.108
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Reports

Congenital Heart Disease Caused by Mutations in the Transcription Factor NKX2-5

Jean-Jacques Schott, * D. Woodrow Benson, *dagger Craig T. Basson, ddagger William Pease, G. Michael Silberbach, Jeffrey P. Moak, Barry J. Maron, Christine E. Seidman, J. G. Seidman §

Mutations in the gene encoding the homeobox transcription factor NKX2-5 were found to cause nonsyndromic, human congenital heart disease. A dominant disease locus associated with cardiac malformations and atrioventricular conduction abnormalities was mapped to chromosome 5q35, where NKX2-5, a Drosophila tinman homolog, is located. Three different NKX2-5 mutations were identified. Two are predicted to impair binding of NKX2-5 to target DNA, resulting in haploinsufficiency, and a third potentially augments target-DNA binding. These data indicate that NKX2-5 is important for regulation of septation during cardiac morphogenesis and for maturation and maintenance of atrioventricular node function throughout life.

J.-J. Schott and J. G. Seidman, Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA. D. W. Benson, C. T. Basson, C. E. Seidman, Cardiovascular Division and Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA. W. Pease, Harrisburg Hospital, Harrisburg, PA 17104, USA. G. M. Silberbach, Division of Pediatric Cardiology, Oregon Health Science University, Portland, OR 97201, USA. J. P. Moak, Division of Pediatric Cardiology, Children's National Medical Center, Washington, DC 20010, USA. B. J. Maron, Minneapolis Heart Institute Foundation, Minneapolis, MN 55407, USA.
*   These authors contributed equally to this work.

dagger    Present address: Cardiovascular Genetics, Medical University of South Carolina, Charleston, SC 29451, USA.

ddagger    Present address: Cardiovascular Division, Cornell University Medical College, New York, NY 10021, USA.

§   To whom correspondence should be addressed. E-mail: seidman{at}rascal.med.harvard.edu

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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S. Caputo, G. Capozzi, M. G. Russo, T. Esposito, L. Martina, D. Cardaropoli, C. Ricci, P. Argiento, G. Pacileo, and R. Calabro (2005)
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   Abstract »    Full Text »    PDF »
Complex cardiac Nkx2-5 gene expression activated by noggin-sensitive enhancers followed by chamber-specific modules.
X. Chi, P. K. Chatterjee, W. Wilson III, S.-X. Zhang, F. J. DeMayo, and R. J. Schwartz (2005)
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   Abstract »    Full Text »    PDF »
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D. Beis, T. Bartman, S.-W. Jin, I. C. Scott, L. A. D'Amico, E. A. Ober, H. Verkade, J. Frantsve, H. A. Field, A. Wehman, et al. (2005)
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   Abstract »    Full Text »    PDF »
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B. B. Keller (2005)
Am J Physiol Heart Circ Physiol 289, H975-H976
   Full Text »    PDF »
Susceptibility genes and modifiers for cardiac arrhythmias.
S. Kaab and E. Schulze-Bahr (2005)
Cardiovasc Res 67, 397-413
   Abstract »    Full Text »    PDF »
Forced myocardin expression primes cardiac and smooth muscle transcription patterning in human mesenchymal stem cells.
C. Ventura (2005)
Cardiovasc Res 67, 182-183
   Full Text »    PDF »
Hand is a direct target of Tinman and GATA factors during Drosophila cardiogenesis and hematopoiesis.
Z. Han and E. N. Olson (2005)
Development 132, 3525-3536
   Abstract »    Full Text »    PDF »
Recent Advances in Cardiac Development With Therapeutic Implications for Adult Cardiovascular Disease.
J. A. Epstein and M. S. Parmacek (2005)
Circulation 112, 592-597
   Full Text »    PDF »
Functional dissection of sequence-specific NKX2-5 DNA binding domain mutations associated with human heart septation defects using a yeast-based system.
A. Inga, S. M. Reamon-Buettner, J. Borlak, and M. A. Resnick (2005)
Hum. Mol. Genet. 14, 1965-1975
   Abstract »    Full Text »    PDF »
Congenital heart disease reminiscent of partial trisomy 2p syndrome in mice transgenic for the transcription factor Lbh.
K. J. Briegel, H. S. Baldwin, J. A. Epstein, and A. L. Joyner (2005)
Development 132, 3305-3316
   Abstract »    Full Text »    PDF »
Identification and analysis of vnd/NK-2 homeodomain binding sites in genomic DNA.
L.-H. Wang, R. Chmelik, D. Tang, and M. Nirenberg (2005)
PNAS 102, 7097-7102
   Abstract »    Full Text »    PDF »
Tbx20 dose-dependently regulates transcription factor networks required for mouse heart and motoneuron development.
J. K. Takeuchi, M. Mileikovskaia, K. Koshiba-Takeuchi, A. B. Heidt, A. D. Mori, E. P. Arruda, M. Gertsenstein, R. Georges, L. Davidson, R. Mo, et al. (2005)
Development 132, 2463-2474
   Abstract »    Full Text »    PDF »
Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation.
F. A. Stennard, M. W. Costa, D. Lai, C. Biben, M. B. Furtado, M. J. Solloway, D. J. McCulley, C. Leimena, J. I. Preis, S. L. Dunwoodie, et al. (2005)
Development 132, 2451-2462
   Abstract »    Full Text »    PDF »
Understanding Conduction System Development: A Hop, Skip and Jump Away?.
G. I. Fishman (2005)
Circ. Res. 96, 809-811
   Full Text »    PDF »
Homeobox Protein Hop Functions in the Adult Cardiac Conduction System.
F. A. Ismat, M. Zhang, H. Kook, B. Huang, R. Zhou, V. A. Ferrari, J. A. Epstein, and V. V. Patel (2005)
Circ. Res. 96, 898-903
   Abstract »    Full Text »    PDF »
Migfilin and its binding partners: from cell biology to human diseases.
C. Wu (2005)
J. Cell Sci. 118, 659-664
   Abstract »    Full Text »    PDF »
Spectrum of atrial septal defects associated with mutations of NKX2.5 and GATA4 transcription factors.
A Sarkozy, E Conti, C Neri, R D'Agostino, M C Digilio, G Esposito, A Toscano, B Marino, A Pizzuti, and B Dallapiccola (2005)
J. Med. Genet. 42, e16
   Full Text »    PDF »
Mechanisms of inherited cardiac conduction disease.
J. P.P. Smits, M. W. Veldkamp, and A. A.M. Wilde (2005)
Europace 7, 122-137
   Abstract »    Full Text »    PDF »
Electrophysiology and anatomy of embryonic rabbit hearts before and after septation.
F. Rothenberg, V. P. Nikolski, M. Watanabe, and I. R. Efimov (2005)
Am J Physiol Heart Circ Physiol 288, H344-H351
   Abstract »    Full Text »    PDF »
ENU induced mutations causing congenital cardiovascular anomalies.
Q. Yu, Y. Shen, B. Chatterjee, B. H. Siegfried, L. Leatherbury, J. Rosenthal, J. F. Lucas, A. Wessels, C. F. Spurney, Y.-J. Wu, et al. (2004)
Development 131, 6211-6223
   Abstract »    Full Text »    PDF »
Thyroid Development and Its Disorders: Genetics and Molecular Mechanisms.
M. De Felice and R. Di Lauro (2004)
Endocr. Rev. 25, 722-746
   Abstract »    Full Text »    PDF »
Molecular basis of AV block and cardiac malformations.
C. Mittmann (2004)
Cardiovasc Res 64, 1-2
   Full Text »    PDF »
Biochemical analyses of eight NKX2.5 homeodomain missense mutations causing atrioventricular block and cardiac anomalies.
H. Kasahara and D. W. Benson (2004)
Cardiovasc Res 64, 40-51
   Abstract »    Full Text »    PDF »
The small heart Mutation Reveals Novel Roles of Na+/K+-ATPase in Maintaining Ventricular Cardiomyocyte Morphology and Viability in Zebrafish.
S. Yuan and E. M. Joseph (2004)
Circ. Res. 95, 595-603
   Abstract »    Full Text »    PDF »
Somatic NKX2-5 mutations as a novel mechanism of disease in complex congenital heart disease.
S M Reamon-Buettner and J Borlak (2004)
J. Med. Genet. 41, 684-690
   Abstract »    Full Text »    PDF »
Transcriptional Regulation of Cardiac Progenitor Cell Populations.
A. M. Masino, T. D. Gallardo, C. A. Wilcox, E. N. Olson, R. S. Williams, and D. J. Garry (2004)
Circ. Res. 95, 389-397
   Abstract »    Full Text »    PDF »
GATA transcription factors in the developing and adult heart.
S. Pikkarainen, H. Tokola, R. Kerkela, and H. Ruskoaho (2004)
Cardiovasc Res 63, 196-207
   Abstract »    Full Text »    PDF »
A novel GATA4 mutation completely segregated with atrial septal defect in a large Japanese family.
A Okubo, O Miyoshi, K Baba, M Takagi, K Tsukamoto, A Kinoshita, K Yoshiura, T Kishino, T Ohta, N Niikawa, et al. (2004)
J. Med. Genet. 41, e97
   Full Text »    PDF »
Characterization of embryonic cardiac pacemaker and atrioventricular conduction physiology in Xenopus laevis using noninvasive imaging.
H. L. Bartlett, T. D. Scholz, F. S. Lamb, and D. L. Weeks (2004)
Am J Physiol Heart Circ Physiol 286, H2035-H2041
   Abstract »    Full Text »    PDF »
Novel NKX2-5 Mutations in Diseased Heart Tissues of Patients with Cardiac Malformations.
S. M. Reamon-Buettner, H. Hecker, K. Spanel-Borowski, S. Craatz, E. Kuenzel, and J. Borlak (2004)
Am. J. Pathol. 164, 2117-2125
   Abstract »    Full Text »    PDF »
BMP10 is essential for maintaining cardiac growth during murine cardiogenesis.
H. Chen, S. Shi, L. Acosta, W. Li, J. Lu, S. Bao, Z. Chen, Z. Yang, M. D. Schneider, K. R. Chien, et al. (2004)
Development 131, 2219-2231
   Abstract »    Full Text »    PDF »
Differential Expression and Function of Tbx5 and Tbx20 in Cardiac Development.
T. F. Plageman Jr. and K. E. Yutzey (2004)
J. Biol. Chem. 279, 19026-19034
   Abstract »    Full Text »    PDF »
Development Gone Awry: Congenital Heart Disease.
P. J. Gruber and J. A. Epstein (2004)
Circ. Res. 94, 273-283
   Abstract »    Full Text »    PDF »
A novel LIM protein Cal promotes cardiac differentiation by association with CSX/NKX2-5.
H. Akazawa, S. Kudoh, N. Mochizuki, N. Takekoshi, H. Takano, T. Nagai, and I. Komuro (2004)
J. Cell Biol. 164, 395-405
   Abstract »    Full Text »    PDF »
NKX2.5 mutations in patients with congenital heart disease.
D. B. McElhinney, E. Geiger, J. Blinder, D. Woodrow Benson, and E. Goldmuntz (2003)
J. Am. Coll. Cardiol. 42, 1650-1655
   Abstract »    Full Text »    PDF »
JUMONJI, a Critical Factor for Cardiac Development, Functions as a Transcriptional Repressor.
T.-G. Kim, J. C. Kraus, J. Chen, and Y. Lee (2003)
J. Biol. Chem. 278, 42247-42255
   Abstract »    Full Text »    PDF »
Cardiac Chamber Formation: Development, Genes, and Evolution.
A. F. M. MOORMAN and V. M. CHRISTOFFELS (2003)
Physiol Rev 83, 1223-1267
   Abstract »    Full Text »    PDF »
Patterns of recurrence of congenital heart disease: An analysis of 6,640 consecutive pregnancies evaluated by detailed fetal echocardiography.
H. K. Gill, M. Splitt, G. K. Sharland, and J. M. Simpson (2003)
J. Am. Coll. Cardiol. 42, 923-929
   Abstract »    Full Text »    PDF »
Induction of cardiomyocytes by GATA4 in Xenopus ectodermal explants.
B. V. Latinkic, S. Kotecha, and T. J. Mohun (2003)
Development 130, 3865-3876
   Abstract »    Full Text »    PDF »
The Different Cardiac Expression of the Type 2 Iodothyronine Deiodinase Gene between Human and Rat Is Related to the Differential Response of the dio2 Genes to Nkx-2.5 and GATA-4 Transcription Factors.
M. Dentice, C. Morisco, M. Vitale, G. Rossi, G. Fenzi, and D. Salvatore (2003)
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   Abstract »    Full Text »    PDF »
Csm, a Cardiac-specific Isoform of the RNA Helicase Mov10l1, Is Regulated by Nkx2.5 in Embryonic Heart.
T. Ueyama, H. Kasahara, T. Ishiwata, N. Yamasaki, and S. Izumo (2003)
J. Biol. Chem. 278, 28750-28757
   Abstract »    Full Text »    PDF »
PITX2 Isoform-specific Regulation of Atrial Natriuretic Factor Expression: SYNERGISM AND REPRESSION WITH Nkx2.5.
M. Ganga, H. M. Espinoza, C. J. Cox, L. Morton, T. A. Hjalt, Y. Lee, and B. A. Amendt (2003)
J. Biol. Chem. 278, 22437-22445
   Abstract »    Full Text »    PDF »
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D. A. Elliott, E. P. Kirk, T. Yeoh, S. Chandar, F. McKenzie, P. Taylor, P. Grossfeld, D. Fatkin, O. Jones, P. Hayes, et al. (2003)
J. Am. Coll. Cardiol. 41, 2072-2076
   Abstract »    Full Text »    PDF »
Electrophysiological phenotyping in genetically engineered mice.
C. I. Berul (2003)
Physiol Genomics 13, 207-216
   Abstract »    Full Text »    PDF »
Cardiac specific differentiation of mouse embryonic stem cells.
A. Sachinidis, B. K. Fleischmann, E. Kolossov, M. Wartenberg, H. Sauer, and J. Hescheler (2003)
Cardiovasc Res 58, 278-291
   Abstract »    Full Text »    PDF »
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C. Ventura, E. Zinellu, E. Maninchedda, M. Fadda, and M. Maioli (2003)
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   Abstract »    Full Text »    PDF »
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Y. Sakata, C. N. Kamei, H. Nakagami, R. Bronson, J. K. Liao, and M. T. Chin (2002)
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   Abstract »    Full Text »    PDF »
Two novel frameshift mutations in NKX2.5 result in novel features including visceral inversus and sinus venosus type ASD.
Y Watanabe, D W Benson, S Yano, T Akagi, M Yoshino, and J C Murray (2002)
J. Med. Genet. 39, 807-811
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Early Signals in Cardiac Development.
S. Zaffran and M. Frasch (2002)
Circ. Res. 91, 457-469
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Cooperative interaction between GATA5 and NF-ATc regulates endothelial-endocardial differentiation of cardiogenic cells.
G. Nemer and M. Nemer (2002)
Development 129, 4045-4055
   Abstract »    Full Text »    PDF »
Osteopenia and male-specific sudden cardiac death in mice lacking a zinc transporter gene, Znt5.
K. Inoue, K. Matsuda, M. Itoh, H. Kawaguchi, H. Tomoike, T. Aoyagi, R. Nagai, M. Hori, Y. Nakamura, and T. Tanaka (2002)
Hum. Mol. Genet. 11, 1775-1784
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Csx/Nkx2-5 Is Required for Homeostasis and Survival of Cardiac Myocytes in the Adult Heart.
H. Toko, W. Zhu, E. Takimoto, I. Shiojima, Y. Hiroi, Y. Zou, T. Oka, H. Akazawa, M. Mizukami, M. Sakamoto, et al. (2002)
J. Biol. Chem. 277, 24735-24743
   Abstract »    Full Text »    PDF »
Perspective: Cardiovascular Disease in the Postgenomic Era--Lessons Learned and Challenges Ahead.
J. A. Epstein, D. J. Rader, and M. S. Parmacek (2002)
Endocrinology 143, 2045-2050
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Cooperative action of Tbx2 and Nkx2.5 inhibits ANF expression in the atrioventricular canal: implications for cardiac chamber formation.
P. E.M.H. Habets, A. F.M. Moorman, D. E.W. Clout, M. A. van Roon, M. Lingbeek, M. van Lohuizen, M. Campione, and V. M. Christoffels (2002)
Genes & Dev. 16, 1234-1246
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AMP-activated protein kinase and familial Wolff-Parkinson-White syndrome: new perspectives on heart development and arrhythmogenesis.
M.H. Gollob and R. Roberts (2002)
Eur. Heart J. 23, 679-681
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Transcriptional Regulation of Vertebrate Cardiac Morphogenesis.
B. G. Bruneau (2002)
Circ. Res. 90, 509-519
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A Population-Based Study on the Frequency of Additional Congenital Malformations in Infants with Congenital Hypothyroidism: Data from the Italian Registry for Congenital Hypothyroidism (1991-1998).
A. Olivieri, M. A. Stazi, P. Mastroiacovo, C. Fazzini, E. Medda, A. Spagnolo, S. De Angelis, M. E. Grandolfo, D. Taruscio, V. Cordeddu, et al. (2002)
J. Clin. Endocrinol. Metab. 87, 557-562
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Regulation of Cardiac Growth and Development by SRF and Its Cofactors.
D. WANG, R. PASSIER, Z.-P. LIU, C.H. SHIN, Z. WANG, S. LI, L.B. SUTHERLAND, E. SMALL, P.A. KRIEG, and E.N. OLSON (2002)
Cold Spring Harb Symp Quant Biol 67, 97-106
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