A case mimicking CS with SOS1 T158A substitution, which has not been reported previously in CS, revealed the complex relationship between the genotype and phenotype of overlapping syndromes of the RAS/RAF/MEK/ERK pathway.
Molecular and clinical analysis of RAF1 in Noonan syndrome and related disorders: dephosphorylation of serine 259 as the essential mechanism for mutant activation.
Remarkably, our cohort of individuals with KRAS mutations showed a high clinical variability, ranging from Noonan syndrome to CFC, and also included two patients who met the clinical criteria of Costello syndrome.
We report on a novel KRAS gene mutation in a patient presenting the clinical features typical of Costello syndrome and the additional findings seen in Noonan syndrome.
Patients with the HRAS mutation c.173C>T (p.T58I) might go undiagnosed because of the milder phenotype compared with other mutations causing Costello syndrome.
Panel testing for rasopathies identified a novel HRAS mutation (c.179G>A; p.Gly60Asp) in three individuals with attenuated features of Costello syndrome.
Costello syndrome (CS) is a rare genetic disorder caused, in the majority of cases, by germline missense HRAS mutations affecting Gly(12) promoting enhanced signaling through the MAPK and PI3K-AKT signaling cascades.