Germline RBBP6 mutations in familial myeloproliferative neoplasms.

We have identified germline RBBP6 mutations in ∼5% of familial MPN cases (3/67) and in ∼0.6% of sporadic cases (3/490) where family history is unknown. The low penetrance present in MPN pedigrees suggests that the disease is triggered by some stochastic factors, perhaps the acquisition of somatic mutations. In addition, common germline predisposition factors, such as JAK2 GGCC haplotype and TERT rs2736100 SNP, seem to have an additive effect on the MPN risk in RBBP6 mutation carriers.