A novel HRAS c.466C>T p.(Phe156Leu) variant in two patients with attenuated features of Costello syndrome.

ABSTRACT: Costello syndrome (CS) is caused by heterozygous HRAS germline mutations. Most patients share the HRAS variant p.Gly12Ser that is associated with a typical, homogeneous phenotype. Rarer pathogenic HRAS variants (e.g., p.Thr56Ile) were identified in individuals with attenuated CS phenotypes. The obvious phenotypical variability reflects different dysfunctional consequences of distinct HRAS variants. We report on two boys with the novel de novo HRAS variant c.466 C > T p.(Phe156Leu). Both had severe feeding difficulties, airway obstruction and developmental delay, which are typical findings in CS. They showed subtle facial and dermatologic features consistent with attenuated CS. They significantly differed in their musculoskeletal, cardiovascular and endocrinologic manifestations underscorin

SUBMITTER: Lindsey-Temple S 

PROVIDER: S-EPMC9437031 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature