Another Gene Added to the List for Noonan Syndrome

Mutations in the SOS1 gene cause 15% to 20% of Noonan syndrome cases.

Noonan syndrome is an autosomal dominant developmental disorder characterized by congenital heart disease (particularly pulmonary stenosis), short stature, learning problems, characteristic facies, and increased risk for leukemia. Affected individuals often have a deformed pectus, with the top part of the sternum protruding and the bottom part being depressed. About 50% of Noonan syndrome cases are due to a gain-of-function mutation in the PTPN11 gene. This gene encodes the tyrosine phosphatase SHP2, which activates the RAS-ERK mitogen-activated protein kinase (MAPK) signal transduction pathway.

The discovery of the PTPN11 mutation in Noonan syndrome prompted a search for similar conditions involving genes in this signal transduction cascade…

Reviewing Author

Judith G. Hall, OC, MD