Title:Novel Variants of DOCK8 Deficiency in a Case Series of Iranian Patients
Volume: 22
Issue: 1
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 and Nima Rezaei*
Affiliation:
- Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University
of Medical Sciences, Tehran, Iran
Keywords:
Dedicator of cytokinesis 8, Job Syndrome, Hyperimmunoglobulinemia E Syndrome, Immunologic Deficiency Syndromes, Primary Immunodeficiency Diseases.
Abstract: 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) were 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 the risk of
aneurysms in these patients, which have been rarely reported in these patients.
