Early-lethal Costello syndrome due to rare HRAS Tandem Base substitution (c.35_36GC>AA; p.G12E)-associated pulmonary vascular disease.

ABSTRACT: Costello syndrome is a rare, autosomal-dominant syndrome caused by activating missense mutations in the Harvey rat sarcoma viral oncogene homolog (HRAS), most often p.G12S. Several rare mutations have consistently been associated with a more severe phenotype that is often lethal in infancy. Cause of death is most often respiratory failure, with hypertrophic cardiomyopathy playing a significant role in morbidity. Impaired fibroblast elastogenesis is thought to contribute to the Costello phenotype, but reports of histologic evidence of disordered elastogenesis at autopsy are limited. We report a patient with Costello syndrome due to a rare tandem base substitution (c.35_36GC>AA) resulting in the p.G12E missense change. The proband died at the age of 3 months from respiratory failure, with mi

SUBMITTER: Weaver KN 

PROVIDER: S-EPMC4294968 | biostudies-literature | 2014 Nov-Dec

REPOSITORIES: biostudies-literature