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

2017; Elsevier BV; Volume: 141; Issue: 4 Linguagem: Inglês

10.1016/j.jaci.2017.06.049

1097-6825

Hassan Abolhassani, Janet Chou, Wayne Bainter, Craig D. Platt, Mahmood Tavassoli, Tooba Momen, Marzieh Tavakol, Mohammad Hossein Eslamian, Mohammad Gharagozlou, Masoud Movahedi, Mohsen Ghadami, Amir Ali Hamidieh, Gholamreza Azizi, Reza Yazdani, Mohsen Afarideh, Alireza Ghajar, Arash Havaei, Zahra Chavoshzadeh, Seyed Alireza Mahdaviani, Taher Cheraghi, Nasrin Behniafard, Reza Amin, Soheila Aleyasin, Reza Faridhosseini, Farahzad Jabbari Azad, Mohammad Nabavi, Mohammad Hassan Bemanian, Saba Arshi, Rasol Molatefi, Roya Sherkat, Mahboubeh Mansouri, Mehrnaz Mesdaghi, Delara Babaie, Iraj Mohammadzadeh, Javad Ghaffari, Alireza Shafiei, Najmeddin Kalantari, Hamid Ahanchian, Maryam Khoshkhui, Habib Soheili, Abbas Dabbaghzadeh, Afshin Shirkani, Rasoul Nasiri Kalmarzi, Seyed Hamidreza Mortazavi, Javad Tafaroji, Abbas Khalili, Javad Mohammadi, Babak Negahdari, Mohammad Taghi Joghataei, Basel K. al-Ramadi, Capucine Pïcard, Nima Parvaneh, Nima Rezaei, Talal A. Chatila, Michel J. Massaad, Sevgi Keleş, Lennart Hammarström, Raif S. Geha, Asghar Aghamohammadi,

Cystic Fibrosis Research Advances

BackgroundCombined 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.ObjectivesThis study aims to characterize the categories of patients with CIDs in Iran clinically and genetically.MethodsClinical 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.ResultsThe 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.ConclusionsThis 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.