A novel germline JAK2 mutation in familial myeloproliferative neoplasms.

The novel H608N mutation is mapped in exon 14, as the classic V617F mutation. Histidine 608 belongs to the JH2 domain of JAK2 protein, which inhibits the JH1 kinase domain. Mutations affecting the JH2 domain, as H608N, might impair the regulatory function of JH2 and increase the kinase activity.

Two cases of hereditary thrombocytosis associated with novel JAK2 germline mutations (R564Q and V617I) have been recently reported. According to these previous reports and to our study, it seems that JAK2 germline mutations might account for some cases of familial ET that are indeed hereditary thrombocytosis.