Molecular characterization of Chilean patients with a clinical diagnosis of Noonan syndrome

Abstract

Noonan syndrome (NS) is an autosomal dominant syndrome characterized by typical dysmorphic features, cardiac anomalies as well as postnatal growth retardation, and is associated with Ras-MAPK pathway gene mutations. The purpose of this study was to improve the diagnosis of Chilean patients with suspected NS through molecular analysis. We screened 18 Chilean patients with a clinical diagnosis of NS for mutations in PTPN11 by high resolution melting (HRM) and subsequent sequencing. Three PTPN11 missense mutations were detected in 22% of analyzed patients. Of these, two (c.181G>A and c.1510A>G) were previously reported and one was the novel substitution c.328G>A (p.E110K) affecting the linker stretch between the N-SH2 and C-SH2 domains of SHP-2 protein. Molecular studies confirmed the clinical diagnosis of NS in 4 of 18 patients, which provided support for therapeutic decisions and improved genetic counseling for their families.