Display options
Cite
Hernández-Porras I, Jiménez-Catalán B, Schuhmacher AJ, et al. The impact of the genetic background in the Noonan syndrome phenotype induced by K-Ras(V14I). Rare Dis. 2015;3(1):e1045169doi: 10.1080/21675511.2015.1045169.
Hernández-Porras, I., Jiménez-Catalán, B., Schuhmacher, A. J., & Guerra, C. (2015). The impact of the genetic background in the Noonan syndrome phenotype induced by K-Ras(V14I). Rare diseases (Austin, Tex.), 3(1), e1045169. https://doi.org/10.1080/21675511.2015.1045169
Hernández-Porras, Isabel, et al. "The impact of the genetic background in the Noonan syndrome phenotype induced by K-Ras(V14I)." Rare diseases (Austin, Tex.) vol. 3,1 (2015): e1045169. doi: https://doi.org/10.1080/21675511.2015.1045169
Hernández-Porras I, Jiménez-Catalán B, Schuhmacher AJ, Guerra C. The impact of the genetic background in the Noonan syndrome phenotype induced by K-Ras(V14I). Rare Dis. 2015 May 22;3(1):e1045169. doi: 10.1080/21675511.2015.1045169. eCollection 2015. PMID: 26458870; PMCID: PMC4590006.
Copy Download .nbib Format: NLM
Share it on

Rare Dis. 2015 May 22;3(1):e1045169. doi: 10.1080/21675511.2015.1045169. eCollection 2015.

The impact of the genetic background in the Noonan syndrome phenotype induced by K-Ras(V14I).

Rare diseases (Austin, Tex.)

Isabel Hernández-Porras, Beatriz Jiménez-Catalán, Alberto J Schuhmacher, Carmen Guerra

Affiliations

  1. Molecular Oncology; Centro Nacional de Investigaciones Oncológicas (CNIO) ; Madrid, Spain.

PMID: 26458870 PMCID: PMC4590006 DOI: 10.1080/21675511.2015.1045169

Abstract

Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by short stature, craniofacial dysmorphism, and congenital heart defects. A significant fraction of NS-patients also develop myeloproliferative disorders. The penetrance of these defects varies considerably among patients. In this study, we have examined the effect of 2 genetic backgrounds (C57BL/6J.OlaHsd and 129S2/SvPasCrl) on the phenotypes displayed by a mouse model of NS induced by germline expression of the mutated K-Ras (V14I) allele, one of the most frequent NS-KRAS mutations. Our results suggest the presence of genetic modifiers associated to the genetic background that are essential for heart development and function at early stages of postnatal life as well as in the severity of the haematopoietic alterations.

Keywords: Noonan Syndrome; Ras oncogenes; Rasopathies; developmental disorders; genetic backgrounds; genotype-phenotype correlation; modifiers; mouse models

References

  1. Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4736-41 - PubMed
  2. Mol Cell Biol. 2012 Oct;32(19):3872-90 - PubMed
  3. Genet Epidemiol. 2002 Aug;23(2):150-64 - PubMed
  4. Am J Med Genet A. 2004 Nov 1;130A(4):378-83 - PubMed
  5. Am J Hum Genet. 1993 Aug;53(2):305-13 - PubMed
  6. Expert Rev Mol Med. 2008 Dec 09;10:e37 - PubMed
  7. Nat Rev Cancer. 2007 Apr;7(4):295-308 - PubMed
  8. J Clin Invest. 2011 Mar;121(3):1009-25 - PubMed
  9. J Pediatr. 2011 Dec;159(6):1029-35 - PubMed
  10. Curr Biol. 1996 May 1;6(5):614-7 - PubMed
  11. Proc Natl Acad Sci U S A. 2014 Nov 18;111(46):16395-400 - PubMed
  12. J Med Genet. 2007 Oct;44(10):651-6 - PubMed
  13. Am J Hum Genet. 2002 Jun;70(6):1555-63 - PubMed
  14. Mamm Genome. 2009 Apr;20(4):214-23 - PubMed
  15. Nat Genet. 1997 May;16(1):19-27 - PubMed
  16. J Pediatr. 2004 Mar;144(3):368-74 - PubMed
  17. PLoS Genet. 2014 Oct 16;10 (10 ):e1004575 - PubMed
  18. Ann N Y Acad Sci. 2010 Dec;1214:99-121 - PubMed
  19. Hum Mol Genet. 2014 Aug 15;23(16):4315-27 - PubMed
  20. Cancer Res. 2006 Jan 1;66(1):62-8 - PubMed
  21. Nat Med. 2006 Mar;12(3):283-5 - PubMed
  22. Hum Mol Genet. 2009 Aug 1;18(15):2768-78 - PubMed
  23. Lancet. 2013 Jan 26;381(9863):333-42 - PubMed
  24. Proc Natl Acad Sci U S A. 2009 May 12;106(19):7979-84 - PubMed
  25. J Clin Invest. 2010 Dec;120(12):4353-65 - PubMed
  26. Am J Med Genet A. 2005 Apr 15;134A(2):165-70 - PubMed
  27. Eur J Med Genet. 2007 Jan-Feb;50(1):43-7 - PubMed
  28. Annu Rev Genomics Hum Genet. 2013;14:355-69 - PubMed
  29. Am J Med Genet A. 2014 Dec;164A(12):3120-5 - PubMed
  30. Rev Esp Cardiol (Engl Ed). 2012 May;65(5):447-55 - PubMed
  31. Am J Med Genet A. 2011 Mar;155A(3):486-507 - PubMed
  32. J Clin Invest. 2008 Jun;118(6):2169-79 - PubMed
  33. Hum Mutat. 2009 Apr;30(4):695-702 - PubMed
  34. Proc Natl Acad Sci U S A. 2011 Mar 22;108(12 ):5015-20 - PubMed
  35. Eur J Hum Genet. 2003 Feb;11(2):201-6 - PubMed
  36. Am J Hum Genet. 2013 Jul 11;93(1):173-80 - PubMed
  37. Best Pract Res Clin Endocrinol Metab. 2011 Feb;25(1):161-79 - PubMed

Publication Types