Molecular characterization using exome sequencing of two probands with the undiagnosed developmental delay from Central Brazil

Abstract

Noonan syndrome (NS) is a heterogeneous autosomal dominant disorder caused by germline mutations in genes belonging RAS-MAPK pathway. Herein, we described two patients with developmental delay and syndromic features from Central Brazil diagnosed with NS using an exome sequencing target gene panel. Germline mutation in genes that participates in the RAS-MAPK signaling pathway are associated with developmental disorders that share particular clinical features such as craniofacial dysmorphisms, congenital heart defects, musculoskeletal and ocular abnormalities, and neurocognitive impairment. The exome sequencing through the intellectual disability gene panel was an effective approach to identify de novo pathogenic mutations in SOS1 and PTPN11 genes that are responsible for Noonan syndrome and was an efficient method to direct the adequate clinical management and better follow-up of the probands and their families.