Identification of a novel de novo deletion in RAF1 associated with biventricular hypertrophy in Noonan syndrome. Issue 8 (29th April 2014)

• Record Type: Journal Article
• Authors: Sana, Maria Elena; Spitaleri, Andrea; Spiliotopoulos, Dimitrios; Pezzoli, Laura; Preda, Laura; Musco, Giovanna; Ferrazzi, Paolo; Iascone, Maria
• Is Part Of: American journal of medical genetics. Volume 164:Issue 8(2014.)
• Page Start: 2069
• Page End: 2073
• Publication Date: 2014-04-29
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36588
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmga36588-sec-0001" sec-type="section"> <p>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 <italic>RAF1</italic> 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. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>