The novel duplication HRAS c.186_206dup p.(Glu62_Arg68dup): clinical and functional aspects.

ABSTRACT: Specific activating missense HRAS variants cause Costello syndrome (CS), a RASopathy with recognizable facial features. The majority of these dominant disease causing variants affect the glycine residues in position 12 or 13. A clinically suspected CS diagnosis can be confirmed through identification of a dominant pathogenic HRAS variant. A novel HRAS variant predicting p.(Glu62_Arg68dup) was identified in an individual with hypertrophic cardiomyopathy, Chiari 1 malformation and ectodermal findings consistent with a RASopathy. Functional studies showed that the p.Glu62_Arg68dup alteration affects HRAS interaction with effector protein PIK3CA (catalytic subunit of phosphoinositide 3-kinase) and the regulator neurofibromin 1 (NF1) GTPase-activating protein (GAP). HRAS^{Glu62_Arg68dup}

SUBMITTER: Gripp KW 

PROVIDER: S-EPMC7576819 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature