After the discovery of germline gain-of-function mutations in PTPN11 (encoding SHP2), the first gene involved in NS and LS (Tartaglia et al., 2001; Digilio et al., 2002; Legius et al., 2002), and of somatic activating mutations in contributing to JMML and acute leukemia (Tartaglia et al., 2003; Jongmans et al., 2011), enormous work was carried out via NGS, which disclosed a plethora of new disease-causing genes and mutations. The gene discussed is PTPN11; the disease is acute leukemia.