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Compound Heterozygous DOCK8 Mutations in a Patient with B Lymphoblastic Leukemia and EBV-Associated Diffuse Large B Cell Lymphoma

Journal of Clinical Immunology volume 39, pages 592–595 (2019)Cite this article

Abstract

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.

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Abbreviations

COG:

Children’s Oncology Group

DLBCL:

diffuse large B cell lymphoma

DOCK8 :

Dedicator of cytokinesis 8

EBV:

Epstein-Barr virus

GVHD:

graft-versus-host disease

HPV:

Human Papilloma Virus

HSCT:

hematopoietic stem cell transplantation

MCV:

Molluscum

VZV:

Varicella Zoster Virus

WES:

whole exome sequencing

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Acknowledgments

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.

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Affiliations

  1. Department of Hematology, Children’s Hospital of Orange County, 1201 W. La Veta Avenue, Orange, CA, 92868, USA

    David Buchbinder

  2. Department of Pediatrics, University of California at Irvine, Orange, CA, USA

    David Buchbinder, Ivan Kirov & Rishikesh S. Chavan

  3. Department of Oncology, Children’s Hospital of Orange County, Orange, CA, USA

    Ivan Kirov & Rishikesh S. Chavan

  4. Laboratory of Clinical Immunology and Microbiology, NIAID, NIH, Bethesda, MD, USA

    Jeffrey Danielson, Alexandra F. Freeman & Helen C. Su

  5. Pediatric Oncology Branch, NCI, NIH, Bethesda, MD, USA

    Nirali N. Shah

Authors
  1. David Buchbinder
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  2. Ivan Kirov
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  3. Jeffrey Danielson
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  4. Nirali N. Shah
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  5. Alexandra F. Freeman
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  6. Rishikesh S. Chavan
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  7. Helen C. Su
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Contributions

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.

Corresponding author

Correspondence to David Buchbinder.

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The authors declared that have no conflict of interest.

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Buchbinder, D., Kirov, I., Danielson, J. et al. Compound Heterozygous DOCK8 Mutations in a Patient with B Lymphoblastic Leukemia and EBV-Associated Diffuse Large B Cell Lymphoma. J Clin Immunol 39, 592–595 (2019). https://doi.org/10.1007/s10875-019-00663-y

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  • DOI: https://doi.org/10.1007/s10875-019-00663-y

Keywords

  • B cell lymphoblastic leukemia
  • diffuse large B cell lymphoma
  • combined immunodeficiency
  • dedicator of cytokinesis 8