Repository of Research and Investigative Information

Repository of Research and Investigative Information

Kurdistan University of Medical Sciences

Clinical, immunologic, and genetic spectrum of 696 patients with combined immunodeficiency

(2018) Clinical, immunologic, and genetic spectrum of 696 patients with combined immunodeficiency. Journal of Allergy and Clinical Immunology.

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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. Objectives: This study aims to characterize the categories of patients with CIDs in Iran clinically and genetically. 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. 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. 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. © 2017 American Academy of Allergy, Asthma & Immunology

Item Type: Article
Keywords: ATM protein; STAT3 protein, Article; child; chromosome deletion 22q11; chromosome deletion 22q11.21; cohort analysis; combined immunodeficiency; consanguinity; demography; diagnostic value; DNA repair; DNA sequence; female; gene mutation; human; hyper IgE syndrome; infant; Iran; Iranian people; laboratory test; major clinical study; male; preschool child; priority journal; school child; survival rate; VDJ recombination
Page Range: pp. 1450-1458
Journal or Publication Title: Journal of Allergy and Clinical Immunology
Volume: 141
Number: 4
Publisher: Mosby Inc.
Identification Number: 10.1016/j.jaci.2017.06.049
ISSN: 00916749
Depositing User: مهندس جمال محمودپور

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