Indeed, the discovery of germline missense mutations in the SHP2-encoding PTPN11 gene in ~50% of NS cases led to the identification of PTPN11 as the most common target of somatic mutations in JMML, a rare, albeit aggressive myelo-proliferative disorder occurring in children, where PTPN11 mutation rates of up to 35% have been reported [196-199]. Here, PTPN11 is linked to juvenile myelomonocytic leukemia.