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Journal of Clinical Immunology

, Volume 39, Issue 6, pp 592–595 | Cite as

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

  • David BuchbinderEmail author
  • Ivan Kirov
  • Jeffrey Danielson
  • Nirali N. Shah
  • Alexandra F. Freeman
  • Rishikesh S. Chavan
  • Helen C. Su
Original 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.

Keywords

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

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

Notes

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.

Authorship 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.

Compliance with Ethical Standards

Conflict of Interest

The authors declared that have no conflict of interest.

Supplementary material

10875_2019_663_MOESM1_ESM.docx (30 kb)
ESM 1 (DOCX 29 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of HematologyChildren’s Hospital of Orange CountyOrangeUSA
  2. 2.Department of PediatricsUniversity of California at IrvineOrangeUSA
  3. 3.Department of OncologyChildren’s Hospital of Orange CountyOrangeUSA
  4. 4.Laboratory of Clinical Immunology and MicrobiologyNIAID, NIHBethesdaUSA
  5. 5.Pediatric Oncology BranchNCI, NIHBethesdaUSA

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