Novel Variants of DOCK8 Deficiency in a Case Series of Iranian Patients

(E-pub Ahead of Print)

Author(s): Sara Momtazmanesh, Elham Rayzan, Samaneh Zoghi, Sepideh Shahkarami, Rasol Molatefi, Iraj Mohammadzadeh, Javad Ghaffari, Hamidreza Mahmoudi, Jasmin Dmytrus, Anna Segarra-Roca, Ido Somekh, Maximilian Witzel, Fabian Hauck, Kaan Boztug, Christoph Klein, Nima Rezaei*

Journal Name: Endocrine, Metabolic & Immune Disorders - Drug Targets
Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders

Become EABM
Become Reviewer
Call for Editor


Background: Dedicator of Cytokinesis 8 (DOCK8) deficiency, the most frequent cause of autosomal recessive hyper immunoglobulin (Ig)E syndrome, is a rare combined immunodeficiency.

Objective: In this study, we report seven patients with consanguineous parents with five novel variants within the DOCK8 gene.

Methods: For genetic analysis, we performed Whole Exome Sequencing (WES), or targeted sequencing by means of Next-generation sequencing (NGS) for some of the patients. For others, Sanger sequencing, Fluorescence-activated cell sorting (FACS), or polymerase chain reaction (PCR) was used.

Results: We report five novel variants within the DOCK8 gene: three deletions (deletion of exons 4-12, 24-30, and 22-27), one frameshift (LRG_196:g.189315dup;p.(Leu1052Profs*7)), and a splice region variant (LRG_196t1:c.741+5G>T). Patients presented with skin lesions, food allergy, candidiasis, otitis, recurrent respiratory infections, short stature, aortic aneurism, gynecomastia, and coarse facial features. Patients had leukocytosis, eosinophilia, lymphopenia, and monocytosis, elevated IgE, IgG, IgA , reduced IgM and IgA levels. Patients had a low percentage of CD3+ and CD4+ cells, and a high percentage of CD19+, CD27+CD19+, and recent thymic emigrants T cells. The percentage of natural killer cells was increased in one of the patients while it was decreased in another patient. One patient died due to disseminated intravascular coagulation after hematopoietic stem cell transplantation.

Conclusion: We reported novel variants within the DOCK8 gene and highlighted risk of aneurysms in these patients, which have been rarely reported in these patients.

Keywords: Dedicator of cytokinesis 8, Job Syndrome, Hyperimmunoglobulinemia E Syndrome, Immunologic Deficiency Syndromes, Primary Immunodeficiency Diseases

Rights & PermissionsPrintExport Cite as

Article Details

Published on: 26 February, 2021
(E-pub Ahead of Print)
DOI: 10.2174/1871530321666210226143912
Price: $95

Article Metrics

PDF: 146