Compound Heterozygous DOCK8 Mutations in a Patient with B Lymphoblastic Leukemia and EBV-Associated Diffuse Large B Cell Lymphoma
Mutations in Dedicator of cytokinesis 8 (DOCK8) are a rare cause of combined immunodeficiency associated with atopy, infectious susceptibility, and risk for malignancy. We describe a 22-year-old male with a diagnosis of B cell lymphoblastic leukemia followed by Epstein-Barr virus (EBV)-associated diffuse large B cell lymphoma (DLBCL) with compound heterozygous mutations in DOCK8 and normal intracellular DOCK8 protein expression. Here, B cell lymphoblastic leukemia followed by EBV-associated DLBCL led to the discovery of DOCK8 deficiency. For instances of high clinical suspicion despite normal DOCK8 protein expression, additional functional testing is critical to make a diagnosis. Understanding the spectrum of DOCK8 mutants and their phenotypes will improve our understanding of DOCK8 deficiency.
KeywordsB cell lymphoblastic leukemia diffuse large B cell lymphoma combined immunodeficiency dedicator of cytokinesis 8
Children’s Oncology Group
diffuse large B cell lymphoma
Dedicator of cytokinesis 8
Human Papilloma Virus
hematopoietic stem cell transplantation
Varicella Zoster Virus
whole exome sequencing
We thank the patient and his family for participating in our research studies, and Pam Angelus for research support. Patient blood samples were obtained after provision of written informed consent under an NIH IRB–approved protocol. This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases.
All authors helped draft and approved the submitted manuscript. HCS and DB coordinated investigation of the patient’s immunological analyses and creation of the manuscript. DB, IK, and RSC diagnosed and treated the patient’s immune disorder. JD and HCS helped characterize the immunological disturbance. NNS, AFF, and HCS helped review the literature and illustrate the manuscript. DB, IK, and RSC recognized the patient’s enigmatic presentation, initiated diagnostic studies, and made possible his multi-institutional investigation.
Compliance with Ethical Standards
Conflict of Interest
The authors declared that have no conflict of interest.