Noonan syndrome is an autosomal dominant disease characterized by dysmorphic 
features, webbed neck, cardiac anomalies, short stature and cryptorchidism. It 
shows phenotypic overlap with Costello syndrome and cardio-facio-cutaneous (CFC) 
syndrome. Noonan syndrome and related disorders are caused by germline mutations 
in genes encoding molecules in the RAS/MAPK pathway. Recently, a 
gain-of-function mutation in SHOC2, p.S2G, has been identified as causative for 
a type of Noonan-like syndrome characterized by the presence of loose anagen 
hair. In order to understand the contribution of SHOC2 mutations to the clinical 
manifestations of Noonan syndrome and related disorders, we analyzed SHOC2 in 92 
patients with Noonan syndrome and related disorders who did not exhibit PTPN11, 
KRAS, HRAS, BRAF, MAP2K1/2, SOS1 or RAF1 mutations. We found the previously 
identified p.S2G mutation in eight of our patients. We developed a rapid 
detection system to identify the p.S2G mutation using melting curve analysis, 
which will be a useful tool to screen for the apparently common mutation. All 
the patients with the p.S2G mutation showed short stature, sparse hair and 
atopic skin. Six of the mutation-positive patients showed severe mental 
retardation and easily pluckable hair, and one showed leukocytosis. No SHOC2 
mutations were identified in leukemia cells from 82 leukemia patients. These 
results suggest that clinical manifestations in SHOC2 mutation-positive patients 
partially overlap with those in patients with typical Noonan or CFC syndrome and 
show that easily pluckable/loose anagen hair is distinctive in SHOC2 
mutation-positive patients.