Case Report of a DDX41 Germline Mutation in a Family with Multiple Relatives Suffering from Leukemia
Jan Nicolai Wagner,
Maximilian Al-Bazaz,
Anika Forstreuter,
Mohammad Ibrahim Hammada,
Jurek Hille,
Dzhoy Papingi,
Carsten Bokemeyer,
Walter Fiedler
Affiliations
Jan Nicolai Wagner
Department of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Maximilian Al-Bazaz
Department of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Anika Forstreuter
Department of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Mohammad Ibrahim Hammada
Department of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Jurek Hille
Department of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Dzhoy Papingi
Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Carsten Bokemeyer
Department of Oncology, Hematology and Bone Marrow Transplantation with Division of Pneumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Walter Fiedler
Department 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.
