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Novel Variants of Dock8 Deficiency in a Case Series of Iranian Patients Publisher Pubmed



Momtazmanesh S1, 2 ; Rayzan E1, 3 ; Zoghi S1, 4, 5 ; Shahkarami S1, 10 ; Molatefi R6 ; Mohammadzadeh I7 ; Ghaffari J8 ; Mahmoudi H9 ; Dmytrus J4, 5 ; Segarraroca A4, 5 ; Somekh I10 ; Witzel M10 ; Hauck F10, 11 ; Boztug K4, 5, 12, 13 Show All Authors
Authors
  1. Momtazmanesh S1, 2
  2. Rayzan E1, 3
  3. Zoghi S1, 4, 5
  4. Shahkarami S1, 10
  5. Molatefi R6
  6. Mohammadzadeh I7
  7. Ghaffari J8
  8. Mahmoudi H9
  9. Dmytrus J4, 5
  10. Segarraroca A4, 5
  11. Somekh I10
  12. Witzel M10
  13. Hauck F10, 11
  14. Boztug K4, 5, 12, 13
  15. Klein C10, 11
  16. Rezaei N1, 2, 14

Source: Endocrine# Metabolic and Immune Disorders - Drug Targets Published:2022


Abstract

Background: Dedicator of Cytokinesis 8 (DOCK8) deficiency, the most frequent cause of autosomal recessive hyper immunoglobulin (Ig)E syndrome, is a rare combined immunodeficien-cy. 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. © 2022 Bentham Science Publishers.
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