Abstrakt
Noonan syndrome (NS) and related disorders are caused by mutations in various genes encoding molecules involved in the RAS-MAPK signalling cascade. There are strong genotype-phenotype correlations.
BRAF is the major gene for cardio-facio-cutaneous syndrome (CFCS), and usually patients with a BRAF mutation have significant cognitive impairment. We report on a patient with LEOPARD syndrome and normal intelligence who was found to carry a novel sequence change in BRAF The mutation p.L245F was demonstrated to be de novo with no evidence of somatic mosaicism.
This observation illustrates that the phenotypic spectrum caused by BRAF mutations is broader than previously assumed and that mental retardation is not necessarily associated. We speculate that the impact of p.L245F on BRAF protein function differs either qualitatively or quantitatively from those mutations associated with CFCS.