A novel germline splice site DDX41 mutation causing MDS/AML.

Abstract

We describe a novel germline mutation in DDX41 causing MDS/AML, and demonstrating recently-appreciated typical features of DDX41 disease including late-onset, preceding cytopenias, normal cytogenetics, and a somatic second-hit DDX41 mutation. Due to longer latency, the familial nature of DDX41-associated MDS/AML is likely under-recognised as it presents at similar age to de novo cases. Nonetheless, recognition is critical for optimising management, including; • genetic counselling/testing of at-risk family members. • screening of any potential related stem cell donors prior to transplant in order to avoid donor-derived leukaemia, an increasingly appreciated risk in germline haematological disease.