New dead/H-Box helicase gene (Ddx41) mutation in an italian family with recurrent leukemia.

Familial clustering of myeloid malignancies with auto- somal dominant (AD) inheritance was firstly recognized in 1999 by the identification of germline mutations asso- ciated with familial platelet disorders and predisposition to myeloid malignancies [1]. Since then, and favored by the introduction of molecular technologies such as next- generation sequencing, a growing number of genes have been associated with AD predisposition to myeloid malig- nancies. These conditions have been recognized by the 2016 revision of World Health Organization (WHO) Classification that emphasized the importance of their identification in the work up of myeloid neoplasms [2]. DDX41 (DEAD/H-Box helicase gene) consists of 17 exons, is located on the long arm of chromosome 5 (5q35.3), and it is characterized by two main domains; the DNA binding DEAD domain and the helicase domain. Familial leukemia with mutated DDX41 displays a pattern of AD inheritance with incomplete penetrance [3,4]. A mutated DDX41, firstly identified in a family with four members affected by AML or MDS [3], is now considered one of the most frequently mutated gene predisposing to myeloid malignancies, and sporadically to chronic myeloid leukemia, non-Hodgkin lymphoma and Hodgkin disease [5]. Mutations have been observed worldwide although differences in the variant type between Caucasian and Asian populations cannot be excluded [6]. Here, we describe an Italian family with a still unde- scribed pathogenetic DDX41 gene mutation in MDS/AML, specifically c.1628C>G p.S543 (rs1581802095) within the helicase C-terminal domain, responsible for the formation of a premature stop codon.