Next-generation sequencing identifies rare variants associated with Noonan syndrome

• DOI: 10.1073/pnas.1324128111
• Publication Date: 2014-07-22T00:59:36Z
• Authors: Peng-Chieh Chen; Jiani Yin; Hui-Wen Yu; Tao Yuan; Minerva Fernandez; Christina K. Yung; Quang M. Trinh; Vanya D. Peltekova; Jeffrey G. Reid; Erica Tworog-Dube; Margaret B. Morgan; Donna M. Muzny; Lincoln Stein; John D. McPherson; Amy E. Roberts; Richard A. Gibbs; Benjamin G. Neel; Raju Kucherlapati
• Keywords: Noonan Syndrome; Costello syndrome; PTPN11

Significance Noonan syndrome (NS) is one of several RASopathies, which are developmental disorders caused by mutations in genes encoding RAS-ERK pathway components. The cause 20–30% NS cases remains unknown, and distinguishing from other RASopathies related can be difficult. We used next-generation sequencing (NGS) to identify causative or candidate for 13 27 patients lacking known NS-associated mutations. Other harbor single variants potential genes, suggesting rare private genetic mechanisms pathogenesis. also found syndromes, together with clinical reevaluation, prompted revision the diagnosis. NGS aid challenging diagnosis young syndromes.