Identification of a novel de novo deletion in RAF1 associated with biventricular hypertrophy in Noonan syndrome
Articolo
Data di Pubblicazione:
2014
Citazione:
Identification of a novel de novo deletion in RAF1 associated with biventricular hypertrophy in Noonan syndrome / M.E. Sana, A. Spitaleri, D. Spiliotopoulos, L. Pezzoli, L. Preda, G. Musco, P. Ferrazzi, M. Iascone. - In: AMERICAN JOURNAL OF MEDICAL GENETICS. PART A. - ISSN 1552-4825. - 164:8(2014), pp. 2069-2073. [10.1002/ajmg.a.36588]
Abstract:
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
14-3-3 protein; Biventricular hypertrophy; Computational modeling; Exome sequencing; Noonan syndrome; RAF1
Elenco autori:
M.E. Sana, A. Spitaleri, D. Spiliotopoulos, L. Pezzoli, L. Preda, G. Musco, P. Ferrazzi, M. Iascone
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