Germline RRAS2 Mutations are not associated with Noonan Syndrome

Mutations in a variety of Ras-MAPK pathway genes are detected in 70-80% of patients with Noonan Syndrome (NS) and related disorders, collectively referred to as RASopathies. Certain patients with RASopathies are predisposed to developing juvenile myelomonocytic leukemia (JMML), a myeloproliferative disorder of early childhood. We recently identified somatic mutations in RRAS2 in JMML and hypothesized that germline RRAS2 mutations could be an additional cause of NS. We therefore screened a cohort of 116 NS patients for mutations in RRAS2 that had no identified lesions. No recurrent mutations were found, ruling out germline mutations in RRAS2 as a cause of Noonan syndrome. (By Dr. Elliot Stieglitz, http://jmg.bmj.com/content/early/2016/04/07/jmedgenet-2016-103889 )