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Case Report of a DDX41 Germline Mutation in a Family with Multiple Relatives Suffering from Leukemia
Jan Nicolai Wagner1, Maximilian Al-Bazaz1, Anika Forstreuter1
1Department of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Introduction:
Previously, it was assumed that genetic influence played a minor role in acute myeloid leukemia (AML). Increasing evidence of germline mutations has emerged, such as DDX41 germline mutation associated with familial AML.
Case Presentation:
A 64-year-old male patient presented with reduced exercise tolerance and shortness of breath. Following confirmation of AML diagnosis, the patient was enrolled into the AMLSG-30-18 study with a requirement for allogenic stem cell transplantation. The sister was initially selected as a fully HLA-matched donor. However, the family history showed risks for familial AML. Due to the striking family history, further diagnostic steps were initiated to detect a germline mutation.
Methods:
Using NGS in the patients' bone marrow AML sample, a DDX41 mutation with a VAF of 49% was detected, raising the possibility of a germline mutation. DNA from cheek swabs and eyebrows were tested for the presence of the DDX41 mutation in all siblings.
Results:
DDX41 germline mutation was detected in 5 out of 6 siblings. The sister was excluded as a related donor and the search for an unrelated donor was initiated.
Conclusion:
Obtaining family history of cancer patients plays a crucial role in oncology. If a germline mutation is suspected, further family work-up should be initiated.
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