A recurrent activating mutation in SHOC2 (p.Ser2Gly) causes Mazzanti syndrome, a RASopathy characterized by features resembling Noonan syndrome and distinctive ectodermal abnormalities.
The entire protein coding sequence of 9 genes implicated in Noonan syndrome and related conditions (PTPN11, SOS1, HRAS, KRAS, NRAS, BRAF, RAF1, MAP2K1, and MAP2K2), together with CBL (exons 8 and 9) and SHOC2 (4A>G), were screened for mutations.
We report on a patient with Noonan syndrome due to SHOC2 missense mutation predicting p.Ser2Gly, recently described in association with Noonan syndrome.
Clinical testing of genes causative of Noonan syndrome and related disorders detected the previously reported, pathogenic, de novo SHOC2 missense mutation predicting p.Ser2Gly.
Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM 607721), recently related to the invariant c.4A>G missense change in SHOC2, is characterized by features reminiscent of Noonan syndrome.