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Clinical, immunologic, and genetic spectrum of 696 patients with combined immunodeficiency.
- Source :
-
The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2018 Apr; Vol. 141 (4), pp. 1450-1458. Date of Electronic Publication: 2017 Sep 12. - Publication Year :
- 2018
-
Abstract
- Background: Combined immunodeficiencies (CIDs) are diseases of defective adaptive immunity with diverse clinical phenotypes. Although CIDs are more prevalent in the Middle East than Western countries, the resources for genetic diagnosis are limited.<br />Objectives: This study aims to characterize the categories of patients with CIDs in Iran clinically and genetically.<br />Methods: Clinical and laboratory data were obtained from 696 patients with CIDs. Patients were subdivided into those with syndromic (344 patients) and nonsyndromic (352 patients) CIDs. Targeted DNA sequencing was performed on 243 (34.9%) patients.<br />Results: The overall diagnostic yield of the 243 sequenced patients was 77.8% (189 patients). The clinical diagnosis of hyper-IgE syndrome (P < .001), onset of disease at greater than 5 years (P = .02), and absence of multiple affected family members (P = .04) were significantly more frequent in the patients without a genetic diagnosis. An autosomal recessive disease was found in 62.9% of patients, reflecting the high rate of consanguinity in this cohort. Mutations impairing VDJ recombination and DNA repair were the most common underlying causes of CIDs. However, in patients with syndromic CIDs, autosomal recessive mutations in ataxia-telangiectasia mutated (ATM), autosomal dominant mutations in signal transducer and activator of transcription 3 (STAT3), and microdeletions in 22q11.21 were the most commonly affected genomic loci. Patients with syndromic CIDs had a significantly lower 5-year survival rate rather than those with nonsyndromic CIDs.<br />Conclusions: This study provides proof of principle for the application of targeted next-generation sequencing panels in countries with limited diagnostic resources. The effect of genetic diagnosis on clinical care requires continued improvements in therapeutic resources for these patients.<br /> (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.)
- Subjects :
- Adolescent
Child
Child, Preschool
Consanguinity
Female
Genes, Recessive genetics
Genes, Recessive immunology
Genetic Predisposition to Disease genetics
High-Throughput Nucleotide Sequencing methods
Humans
Immunologic Deficiency Syndromes mortality
Infant
Iran
Job Syndrome genetics
Job Syndrome immunology
Job Syndrome mortality
Male
Mutation genetics
Mutation immunology
Phenotype
Retrospective Studies
STAT3 Transcription Factor genetics
STAT3 Transcription Factor immunology
Sequence Analysis, DNA methods
Survival Rate
Immunologic Deficiency Syndromes genetics
Immunologic Deficiency Syndromes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-6825
- Volume :
- 141
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of allergy and clinical immunology
- Publication Type :
- Academic Journal
- Accession number :
- 28916186
- Full Text :
- https://doi.org/10.1016/j.jaci.2017.06.049