Identification of a novel de novo deletion in RAF1 associated with biventricular hypertrophy in Noonan syndrome.
Am J Med Genet A
; 164A(8): 2069-73, 2014 Aug.
Article
em En
| MEDLINE
| ID: mdl-24782337
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Deleção de Genes
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Cardiomegalia
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Proteínas Proto-Oncogênicas c-raf
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Estudos de Associação Genética
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Síndrome de Noonan
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article