DDX41 mutations are associated with hematologic malignancies including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but the incidence in idiopathic cytopenia of undetermined significance (ICUS) is unknown. We investigated the incidence, genetic characteristics, and clinical features of DDX41 mutations in Korean patients with ICUS, MDS, or AML. We performed targeted deep sequencing of 61 genes including DDX41 in 457 patients with ICUS (n=75), MDS (n=210), or AML (n=172). The germline DDX41 mutations with causality were identified in 28 (6.1%) patients, of whom 27 (96.4%) had somatic mutations in the other position of DDX41. Germline origins of the DDX41 mutations were confirmed in all of the 11 patients who performed germline-based testing. Of the germline DDX41 mutations, p.V152G (n=10) was most common, followed by p.Y259C (n=8), p.A500fs (n=6), and p.E7* (n=3). Compared with non-mutated patients, DDX41-mutated patients showed male predominance, old age, normal karyotype, low leukocyte count, and hypocellular marrow at diagnosis. Three of the 4 ICUS patients with germline DDX41 mutations progressed to MDS. DDX41 mutations in Korean patients showed a high incidence and distinct mutation patterns, in that p.V152G was a unique germline variant. ICUS harboring germline DDX41 mutations may be regarded as a hereditary myeloid neoplasm. Germline DDX41 mutations are not uncommon and should be explored when treating the patients with myeloid malignancies.

Woo-Jung Songhttps://orcid.org/0000-0002-4630-9922 Tae-Bum Kim https://orcid.org/0000-0001-5663-0640 R E FE R E N C E S 1. Schatz M, Rosenwasser L. The allergic asthma phenotype. J Allergy Clin Immunol Pract. 2014;2:645-648; quiz 649. 2. Romanet-Manent S, Charpin D, Magnan A, Lanteaume A, Vervloet D. Allergic vs nonallergic asthma: what makes the difference? Allergy. 2002;57:607-613. 3. Zissler UM, Esser-von Bieren J, Jakwerth CA, Chaker AM, Schmidt-Weber CB. Current and future biomarkers in allergic asthma. Allergy. 2016;71:475-494. 4. Virchow JC Jr, Kroegel C, Walker C, Matthys H. Cellular and immunological markers of allergic and intrinsic bronchial asthma. Lung. 1994;172:313-334. 5. Subramanian H, Gupta K, Ali H. Roles of Mas-related G protein-coupled receptor X2 on mast cell-mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases. J Allergy Clin Immunol. 2016;138:700-710. 6. Ali H. Mas-related G protein coupled receptor-X2: a potential new target for modulating mast cell-mediated allergic and inflammatory diseases. J Immunobiol. 2016;1:115. 7. Tatemoto K, Nozaki Y, Tsuda R, et al. Immunoglobulin E-independent activation of mast cell is mediated by Mrg receptors. Biochem Biophys Res Commun. 2006;349:1322-1328. 8. Kim TB, Park CS, Bae YJ, Cho YS, Moon HB. Factors associated withseverity and exacerbation of asthma: a baseline analysis of the cohort for reality and evolution of adult asthma in