So far , data from the literature indicate that PTPN11 mutations ssociated with syndromic and non - syndromic JMML / MPD cluster n exon 3 ( 90% ) and 13 ( 10% ) and these represent the only coding ortions of the gene screened in the majority of patients , in both urope and United States [ 2,3 ] .
While the clonal proliferative advantage in on - syndromic JMML cells results from acquired PTPN11 lesions riving to enhanced signal flow through the RAS – MAPK pathay , MPD occurring in NS is associated to a relatively narrow pectrum of germ - line mutations that have less potency in dysreglating this signalling cascade [ 2 ] .
Somatic mutations affecting genes involved in the as - mitogen - activated protein kinase ( MAPK ) pathway are responible for about 80% of JMML ( PTPN11 35% , KRAS / NRAS 25% , CBL 0% , NF1 11% ) [ 1,2 ] .
Germline PTPN11 mutation affecting exon 8 in a case of syndromic juvenile myelomonocytic leukemia .
Instead , germ - line mutations in the PTPN11 ene are responsible for about 50% of Noonan syndrome ( NS ) , a evelopmental disorder that occasionally displays MPD sharing imilarities with JMML .