Abstract

Background: 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. Methods: We screened 18 Chilean patients with a clinical diagnosis of NS for mutations in PTPN11 by high resolution melting (HRM) and subsequent sequencing. Results: 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. Conclusion: 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.