Variable phenotypic expression in a large Noonan syndrome family segregating a novel SOS1 mutation

摘要

Noonan syndrome (NS) is an autosomal dominant multisystem condition with a variable phenotype. The most characteristic features are short stature, congenital heart defects, and recognizable facial features. Mutations in SOS1 are found in 10–20% of patients with NS. Different genotype–phenotype studies mention correlations between SOS1 mutations and some features, such as ectodermal abnormalities and specific facial features. We present a large NS family with a novel pathogenic mutation; SOS1 c.3134CG, p.Pro1045Arg. Ten family members with NS are included with genetically confirmed mutation and clinical evaluation. The phenotype shows a broad spectrum from only few suggestive features for NS in the older generation to typical features in the youngest generation. We report on a novel pathogenic mutation in the SOS1 gene and a large clinical spectrum in a NS family with ten genetically confirmed affected individuals.