Identification of a novel de novo deletion in RAF1 associated with biventricular hypertrophy in Noonan syndrome

Maria Elena Sana, Andrea Spitaleri, Dimitrios Spiliotopoulos, Laura Pezzoli, Laura Preda, Giovanna Musco, Paolo Ferrazzi, Maria Iascone

Research output: Contribution to journalArticlepeer-review


Biventricular hypertrophy (BVH) is a disease state characterized by the thickening of the ventricle walls. The differential diagnosis of BVH with other congenital and familial diseases in which increased ventricle wall thickness is a prominent clinical feature is fundamental due to its therapeutic and prognostic value, mainly during infancy. We describe a 2-month-old infant presenting BVH. Using exome sequencing, we identified a novel de novo 3-bp deletion in the RAF1 gene that is located in the binding active site for the 14-3-3 peptide. Based on docking calculations, we demonstrate that this novel mutation impairs protein/target binding, thus constitutively activating Ras signaling, which is a dysregulation associated with Noonan syndrome. Finally, our study underlines the importance of molecular modeling to understand the roles of novel mutations in pathogenesis.

Original languageEnglish
Pages (from-to)2069-2073
Number of pages5
JournalAmerican Journal of Medical Genetics, Part A
Issue number8
Publication statusPublished - 2014


  • 14-3-3 protein
  • Biventricular hypertrophy
  • Computational modeling
  • Exome sequencing
  • Noonan syndrome
  • RAF1

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Medicine(all)


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