Finally, mutations in the Ptpn11 gene (encoding SHP-2) underlie the developmental disorders Noonan syndrome and Leopard syndrome characterized by congenital heart disease and hematologic abnormalities.
Noonan syndrome is one of the most common causes of human congenital heart disease and is frequently associated with missense mutations in the protein phosphatase SHP-2.
After PTPN11 was identified as a Noonan syndrome disease gene, additional discoveries have made clear that mutations in other genes along the RAS signaling pathway can cause a spectrum of syndromes and possibly isolated congenital heart disease.