Novel Variants of DOCK8 Deficiency in a Case Series of Iranian Patients.
Dedicator of cytokinesis 8
Hyperimmunoglobulinemia E Syndrome
Immunologic Deficiency Syndromes
Job Syndrome
Primary Immunodeficiency Diseases.
Journal
Endocrine, metabolic & immune disorders drug targets
ISSN: 2212-3873
Titre abrégé: Endocr Metab Immune Disord Drug Targets
Pays: United Arab Emirates
ID NLM: 101269157
Informations de publication
Date de publication:
2022
2022
Historique:
received:
29
10
2020
revised:
19
01
2021
accepted:
20
01
2021
pubmed:
27
2
2021
medline:
31
3
2022
entrez:
26
2
2021
Statut:
ppublish
Résumé
Dedicator of Cytokinesis 8 (DOCK8) deficiency, the most frequent cause of autosomal recessive hyper immunoglobulin (Ig)E syndrome, is a rare combined immunodeficiency. In this study, we report seven patients, with consanguineous parents, with five novel variants within the DOCK8 gene. 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. 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. 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.
Sections du résumé
BACKGROUND
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
OBJECTIVE
In this study, we report seven patients, with consanguineous parents, with five novel variants within the DOCK8 gene.
METHODS
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 33634762
pii: EMIDDT-EPUB-114583
doi: 10.2174/1871530321666210226143912
doi:
Substances chimiques
DOCK8 protein, human
0
Guanine Nucleotide Exchange Factors
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
159-168Subventions
Organisme : Tehran University of Medical Sciences
ID : 98-3-205-46257
Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.