A novel start-loss mutation of the SH2B3 gene in a family with myeloproliferative neoplasms

The ever-increasing advances in high-throughput sequencing have broadened our understanding of the genetic pathogenesis of Philadelphia-negative myeloproliferative neoplasms (MPNs). Convergent studies have shown that MPN driver mutations associate with additional mutations found in genes coding for negative regulators of the JAK/STAT signaling, including the SH2B3 (SH2B-adaptor protein 3, also known as LNK). Here, we describe a novel heterozygous start-loss mutation of the SH2B3 gene (c.3G>A, SH2B3(M?)) in a consanguineous family characterized by recurrent early onset of JAK2(V617F)-positive MPNs. The model represented by this pedigree suggests that the SH2B3 could be a predisposing mutation that facilitates the acquisition of driver mutations.