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

Abolhassani, H. and Chou, J. and Bainter, W. and Platt, C. D. and Tavassoli, M. and Momen, T. and Tavakol, M. and Eslamian, M. H. and Gharagozlou, M. and Movahedi, M. and Ghadami, M. and Hamidieh, A. A. and Azizi, G. and Yazdani, R. and Afarideh, M. and Ghajar, A. and Havaei, A. and Chavoshzadeh, Z. and Mahdaviani, S. A. and Cheraghi, T. and Behniafard, N. and Amin, R. and Aleyasin, S. and Faridhosseini, R. and Jabbari-Azad, F. and Nabavi, M. and Bemanian, M. H. and Arshi, S. and Molatefi, R. and Sherkat, R. and Mansouri, M. and Mesdaghi, M. and Babaie, D. and Mohammadzadeh, I. and Ghaffari, J. and Shafiei, A. and Kalantari, N. and Ahanchian, H. and Khoshkhui, M. and Soheili, H. and Dabbaghzadeh, A. and Shirkani, A. and Nasiri Kalmarzi, R. and Mortazavi, S. H. and Tafaroji, J. and Khalili, A. and Mohammadi, J. and Negahdari, B. and Joghataei, M. T. and al-Ramadi, B. K. and Picard, C. and Parvaneh, N. and Rezaei, N. and Chatila, T. A. and Massaad, M. J. and Keles, S. and Hammarström, L. and Geha, R. S. and Aghamohammadi, A. (2018) Clinical, immunologic, and genetic spectrum of 696 patients with combined immunodeficiency. Journal of Allergy and Clinical Immunology, 141 (4). pp. 1450-1458.

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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
Additional Information: Cited By :26 Export Date: 16 February 2020 CODEN: JACIB Correspondence Address: Aghamohammadi, A.; Children's Medical Center Hospital, 62 Qarib St, Keshavarz Blvd, Iran; email:
Uncontrolled Keywords: Combined immunodeficiencies next-generation DNA sequencing targeted gene panel sequencing whole-exome sequencing 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 adolescent genetic predisposition genetics high throughput sequencing immune deficiency immunology mortality mutation phenotype procedures recessive gene retrospective study Child, Preschool Genes, Recessive Genetic Predisposition to Disease High-Throughput Nucleotide Sequencing Humans Immunologic Deficiency Syndromes Job Syndrome Retrospective Studies Sequence Analysis, DNA STAT3 Transcription Factor
Subjects: QW Microbiology and Immunology
QZ pathology-neoplasms-Genetics
Divisions: Mashhad University of Medical Sciences
Depositing User: lib2 lib2 lib2
Date Deposited: 10 Jun 2020 07:02
Last Modified: 10 Jun 2020 07:02

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