Lab Med Online.  2022 Jul;12(3):209-213. 10.47429/lmo.2022.12.3.209.

A Novel Germline Mutation in DDX41 Predisposed to Myelodysplasia/Acute Myeloid Leukemia

• Kwak MS
• Jeong IH
• Kim SH
• Kim N

• KMID: 2538608
• DOI: http://doi.org/10.47429/lmo.2022.12.3.209

Abstract

Germline DDX41lesions indicate a hereditary myelodysplastic syndrome and acute myeloid leukemia (MDS/AML). Canonical somatic mutations in this gene often coincide as a second hit with germline DDX41mutations. We report a patient with inherited MDS/AML containing novel germline DDX41mutations that harbor somatic mutations in the other DDX41allele. The 72-year-old woman was diagnosed with myelodysplastic syndrome with excess blasts-2 (MDS-EB-2) and had gone through 16 rounds of chemotherapy. However, an increase in leukemic myeloblasts was observed in the bone marrow aspiration, resulting in transition to AML. Targeted gene panel sequencing revealed DDX41c.308_309del (p.Glu103Valfs*31) with a variant allele frequency (VAF) of 49%, and DDX41c.1589G>A (p.Gly530Asp) with a VAF of 6%. The c.308_309del variant was confirmed as a germline variant after analyzing buccal DNA. An identical germline DDX41mutation was detected in her unaffected daughter and son. The patient was repeatedly hospitalized for neutropenic fever and eventually expired on account of sepsis. Genetic investigation is crucial for providing appropriate medical management to patients and determining the prognosis of a disease. In addition, it helps to provide appropriate counseling and raise awareness of inherited hematologic malignancies for family members.

Keyword

DEAD box helicase 41; Genetic variations; Myelodysplastic syndromes; Acute myeloid leukemia; Next-generation sequencing

Figure

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  Fig. 1 (A) Family pedigree of the patient. The arrow indicates the proband. Circled dots indicate heterozygous carriers of the germline DDX41 p.(Glu103Valfs*31) variant. Child 2 and 3 refused genetic testing. (B) Electropherogram showing the germline heterozygous c.308_309del variant detected in the peripheral blood sample of the patient. (C) DDX41 protein structure with germline DDX41 variants reported in this case.

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