Skip to main content
Log in

Familial congenital heart disease, progressive atrioventricular block and the cardiac homeobox transcription factor gene NKX2.5:

identification of a novel mutation

  • CLINICAL CORRESPONDENCE
  • Published:
Clinical Research in Cardiology Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  1. Azpiazu N, Frasch M (1993) Tinman and bagpipe: two homeo box genes that determine cell fates in the dorsal mesoderm of Drosophila. Genes Dev 7:1325–1340

    PubMed  CAS  Google Scholar 

  2. 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. J Clin Invest 104:1567–1573

    Article  PubMed  CAS  Google Scholar 

  3. Benson DW (2000) Advances in cardiovascular genetics and embryology: role of transcription factors in congenital heart disease. Curr Opin Pediatr 12:497–500

    Article  PubMed  CAS  Google Scholar 

  4. Biben C, Weber T, Kesteven S, Stanley E, McDonald L, Elliott DA, Barnett L, Koentgen F, Robb L, Feneley M, Harvey RP (2000) Cardiac septal and valvular dysmorphogenesis in mice heterozygous for mutation in the homeobox gene NKX2–5. Circ Res 87:888–895

    PubMed  CAS  Google Scholar 

  5. Clark KL, Yutzey KE, Benson DW (2006) Transcription factors and congenital heart defects. Ann Rev Physiol 68:97–121

    Article  CAS  Google Scholar 

  6. Elliot DA, Kirk EP, Yeoh T, Chandar S, McKenzie F, Taylor P, Grossfeld P, Fatkin D, Jones O, Hayes P, Feneley M, Harvey RP (2003) Cardiac homeobox gene NKX2-5 mutations and congenital heart disease. Associations with atrial septal defect and hypoplastic left heart syndrome. J Am Coll Cardiol 41:2072–2076

    Article  CAS  Google Scholar 

  7. Fishman MC, Olson EN (1997) Parsing the heart: genetic modules for organ assembly. Cell 91(2):153–156

    Article  PubMed  CAS  Google Scholar 

  8. Goldmuntz E, Geiger E, Benson DW (2001) NKX2. 5 mutations in patients with tetralogy of Fallot. Circulation 104:2565–2568

    PubMed  CAS  Google Scholar 

  9. Gutierrez-Roelens I, Sluysmans T, Gewillig M, Devriendt K, Vikkula M (2002) Progessive AV-Block and anomalous venous return among cardiac anomalies associated with two novel missense mutations in the CSX/ NKX2-5 gene. Hum Mutat 20:75–76

    Article  PubMed  CAS  Google Scholar 

  10. Harvey RP (1996) Nk-2 homeobox genes and heart development. Dev Biol 178(2):203–216

    Article  PubMed  CAS  Google Scholar 

  11. Hirayama-Yamada K, Kamisago M, Akimoto K, Aotsuka H, Nakamura Y, Tomita H, Furutani M, Imamura S, Takao A, Nakazawa M, Matsuoka R (2005) Phenotypes with GATA4 or NKX2. 5 mutations in familial atrial septal defect. Am J Med Genet A 135:47–52

    PubMed  Google Scholar 

  12. Hoffman JI, Kaplan S (2002) The incidence of congenital heart disease. J Am Coll Cardiol 39(12):1890–1900

    Article  PubMed  Google Scholar 

  13. Hosoda T, Komuro I, Shiojima I, Hiroi Y, Harada M, Murakawa Y, Hirata Y, Yazaki Y (1999) Familial atrial septal defct and atrioventricular conduction disturbance with a point mutation in the cardiac homeobox gene CSX/NKX2. 5 in a Japanese patient. Jpn Circ J 63:425–426

    Article  PubMed  CAS  Google Scholar 

  14. Ikeda Y, Hiroi Y, Hosoda T, Utsunomiya T, Matsuo S, Ito T, Inoue J, Sumiyoshi T, Takano H, Nagai R, Komuro I (2002) Novel point mutation in the cardiac transcription factor CSX/NKX2. 5 associated with congenital heart disease. Circ J 66:561–563

    Article  PubMed  CAS  Google Scholar 

  15. Jay PY, Harris BS, Maguire CT, Buerger A, Wakimoto H, Tanaka M, Kupershmidt S, Roden DM, Schultheiss TM, O’Brien TX, Gourdie RG, Berul CI, Izumo S (2004) NKX2. 5 mutation causes anatomic hypoplasia of the cardiac conduction system. J Clin Invest 113:1130–1137

    Article  PubMed  CAS  Google Scholar 

  16. Kasahara H, Benson DW (2004) Biochemical analysis of eight NKX2. 5 homeodomain missense mutations causing atrioventricular block and cardiac anomalies. Cardiovasc Res 64:40–51

    Article  PubMed  CAS  Google Scholar 

  17. Köhler F, Fotuhi P, Baumann G (2001) Schwangerschaft und angeborene Herzfehler. Z Kardiol 90 (Suppl 4):30–35

    PubMed  Google Scholar 

  18. McElhinney DB, Geiger E, Blinder J, Benson DW, Goldmuntz E (2003) NKX2. 5 mutations in patients with congenital heart disease. J Am Coll Cardiol 42:1650–1655

    Article  PubMed  CAS  Google Scholar 

  19. Olson EN, Srivastava D (1996) Molecular pathways controlling heart development. Science 272(5262):671–676

    PubMed  CAS  Google Scholar 

  20. Pashmforoush M, Lu JT, Chen H, Amand TS, Kondo R, Pradervand S, Evans SM, Clark B, Feramisco JR, Giles W, Ho SW, Benson DW, Silberbach M, Shou W, Chien KR (2004) NKX2. 5 pathways and congenital heart disease: loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block. Cell 117:373–386

    Article  PubMed  CAS  Google Scholar 

  21. Sarkozy A, Conti E, Neri C, d’Agostino R, Digilio MC, Esposito G, Toscano A, Marino B, Pizzuti A, Dallapiccola B (2005) Spectrum of atrial septal defects associated with mutations of NKX2. 5 and GATA4 transcription factors. J Med Genet 42:e16

    Article  PubMed  CAS  Google Scholar 

  22. Schott JJ, Benson DW, Basson CT, Pease W, Silberbach GM, Moak JP, Maron BJ, Seidman CE, Seidman JG (1998) Congenital heart disease caused by mutations in the transcription factor NKX2. 5. Science 281:108–111

    Article  PubMed  CAS  Google Scholar 

  23. Watanabe Y, Benson DW, Yano S, Akagi T, Yoshino M, Murray JC (2002) Two novel frameshift mutations in NKX2. 5 result in novel features including visceral inversus and sinus venosus type ASD. J Med Genet 39:807–811

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kai König MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

König, K., Will, J.C., Berger, F. et al. Familial congenital heart disease, progressive atrioventricular block and the cardiac homeobox transcription factor gene NKX2.5:. Clin Res Cardiol 95, 499–503 (2006). https://doi.org/10.1007/s00392-006-0412-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00392-006-0412-9

Keywords

Navigation