TY - JOUR
T1 - Identification of a novel de novo deletion in RAF1 associated with biventricular hypertrophy in Noonan syndrome
AU - Sana, Maria Elena
AU - Spitaleri, Andrea
AU - Spiliotopoulos, Dimitrios
AU - Pezzoli, Laura
AU - Preda, Laura
AU - Musco, Giovanna
AU - Ferrazzi, Paolo
AU - Iascone, Maria
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - 14-3-3 protein
KW - Biventricular hypertrophy
KW - Computational modeling
KW - Exome sequencing
KW - Noonan syndrome
KW - RAF1
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U2 - 10.1002/ajmg.a.36588
DO - 10.1002/ajmg.a.36588
M3 - Article
C2 - 24782337
AN - SCOPUS:84904416398
VL - 164
SP - 2069
EP - 2073
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 8
ER -