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

被引：86

作者：

Abolhassani, Hassan ^{[1
,2
,3
]}

Chou, Janet ^{[4
,5
]}

Bainter, Wayne ^{[4
,5
]}

Platt, Craig D. ^{[4
,5
]}

Tavassoli, Mahmood ^{[6
]}

Momen, Tooba ^{[6
]}

Tavakol, Marzieh ^{[7
]}

Eslamian, Mohammad Hossein ^{[8
]}

Gharagozlou, Mohammad ^{[9
,10
]}

Movahedi, Masoud ^{[9
,10
]}

Ghadami, Mohsen ^{[11
]}

Hamidieh, Amir Ali ^{[12
]}

Azizi, Gholamreza ^{[13
]}

Yazdani, Reza ^{[1
,2
,14
,41
]}

Afarideh, Mohsen ^{[1
,2
]}

Ghajar, Alireza ^{[1
,2
]}

Havaei, Arash ^{[1
,2
]}

Chavoshzadeh, Zahra ^{[12
,15
]}

Mahdaviani, Seyed Alireza ^{[16
]}

Cheraghi, Taher ^{[17
]}

Behniafard, Nasrin ^{[18
]}

Amin, Reza ^{[19
]}

Aleyasin, Soheila ^{[19
]}

Faridhosseini, Reza ^{[20
]}

Jabbari-Azad, Farahzad ^{[20
]}

Nabavi, Mohammamd ^{[21
]}

Bemanian, Mohammad Hassan ^{[21
]}

Arshi, Saba ^{[21
]}

Molatefi, Rasol ^{[21
,22
]}

Sherkat, Roya ^{[23
]}

Mansouri, Mahboubeh

Mesdaghi, Mehrnaz ^{[12
,15
]}

Babaie, Delara ^{[12
]}

Mohammadzadeh, Iraj ^{[24
]}

Ghaffari, Javad ^{[25
]}

Shafiei, Alireza ^{[26
]}

Kalantari, Najmeddin ^{[27
]}

Ahanchian, Hamid ^{[20
]}

Khoshkhui, Maryam ^{[20
]}

Soheili, Habib ^{[28
]}

Dabbaghzadeh, Abbas ^{[24
]}

Shirkani, Afshin ^{[29
]}

Kalmarzi, Rasoul Nasiri ^{[30
]}

Mortazavi, Seyed Hamidreza ^{[31
]}

Tafaroji, Javad ^{[5
,32
]}

Khalili, Abbas ^{[33
]}

Mohammadi, Javad ^{[34
]}

Negahdari, Babak ^{[35
]}

Joghataei, Mohammad-Taghi ^{[36
,37
]}

al-Ramadi, Basel K. ^{[38
]}

机构：

[1] Childrens Med Ctr, Pediat Ctr Excellence, Res Ctr Immunodeficiencies, Tehran, Iran

[2] Univ Med Sci, Tehran, Iran

[3] Karolinska Univ, Huddinge Hosp, Karolinska Inst, Div Clin Immunol,Dept Lab Med, Stockholm, Sweden

[4] Harvard Med Sch, Boston Childrens Hosp, Div Immunol, Boston, MA USA

[5] Harvard Med Sch, Dept Pediat, Boston, MA USA

[6] Isfahan Univ Med Sci, Res Inst Primordial Prevent Noncommunicable Dis, Child Growth & Dev Res Ctr, Dept Allergy & Clin Immunol, Esfahan, Iran

[7] Alborz Univ Med Sci, Noncommunicable Dis Res Ctr, Karaj, Iran

[8] Hamadan Univ Med Sci, Dept Pediat, Hamadan, Iran

[9] Childrens Med Ctr, Asthma & Allergy Pediat Ctr Excellence, Dept Immunol, Tehran, Iran

[10] Univ Med Sci, Tehran, Iran

[11] Univ Tehran Med Sci, Dept Med Genet, Tehran, Iran

[12] Univ Tehran Med Sci, Oncol & Stem Cell Transplantat Res Ctr, Hematol, Tehran, Iran

[13] Alborz Univ Med Sci, Imam Hassan Mojtaba Hosp, Dept Lab Med, Karaj, Iran

[14] Isfahan Univ Med Sci, Sch Med, Dept Immunol, Esfahan, Iran

[15] Shahid Beheshti Univ Med Sci, Mofid Childrens Hosp, Pediat Infect Res Ctr, Tehran, Iran

[16] Shahid Beheshti Univ Med Sci, NRITLD, Pediat Resp Dis Res Ctr, Tehran, Iran

[17] Guilan Univ Med Sci, Shahrivar Childrens Hosp 17, Dept Pediat, Rasht, Iran

[18] Shahid Sadoughi Univ Med Sci, Dept Allergy & Clin Immunol, Yazd, Iran

[19] Shiraz Univ Med Sci, Namazi Hosp, Dept Pediat Immunol & Allergy, Shiraz, Iran

[20] Mashhad Univ Med Sci, Dept Allergy & Clin Immunol, Mashhad, Iran

[21] Iran Univ Med Sci, Rasool & Akram Hosp, Dept Allergy & Clin Immunol, Tehran, Iran

[22] Ardabil Univ Med Sci, Bo Ali Childrens Hosp, Dept Pediat, Ardebil, Iran

[23] Isfahan Univ Med Sci, Al Zahra Hosp, Acquired Immunodeficiency Res Ctr, Esfahan, Iran

[24] Babol Univ Med Sci, Amirkola Hosp, Noncommunicable Pediat Dis Res Ctr, Babol Sar, Iran

[25] Mazandaran Univ Med Sci, Dept Pediat, Sari, Iran

[26] Univ Tehran Med Sci, Bahrami Hosp, Dept Immunol, Tehran, Iran

[27] Golestan Univ Med Sci, Dept Immunol & Allergy, Gorgan, Iran

[28] Arak Univ Med Sci, Sch Med, Dept Pediat, Arak, Iran

[29] Bushehr Univ Med Sci, Sch Med, Allergy & Clin Immunol Dept, Bushehr, Iran

[30] Kurdistan Univ Med Sci, Cellular & Mol Res Ctr, Sanandaj, Iran

[31] Kermanshah Univ Med Sci, Dept Pediat, Kermanshah, Iran

[32] Qom Univ Med Sci, Dept Pediat, Qom, Iran

[33] Shahid Sadoughi Univ Med Sci, Dept Pediat, Yazd, Iran

[34] Univ Tehran, Fac New Sci & Technol, Dept Life Sci Engn, Tehran, Iran

[35] Univ Tehran Med Sci, Dept Med Biotechnol, Sch Adv Technol Med, Tehran, Iran

[36] Univ Tehran Med Sci, Sch Med, Cellular & Mol Res Ctr, Tehran, Iran

[37] Univ Tehran Med Sci, Sch Med, Dept Anat & Neurosci, Tehran, Iran

[38] United Arab Univ, Coll Med & Hlth Sci, Dept Med Microbiol & Immunol, Al Ain, U Arab Emirates

[39] Necker Enfants Malades Hosp, AP HP, Study Ctr Primary Immunodeficiencies, Paris, France

[40] USERN, Primary Immunodeficiency Dis Network PIDNet, Tehran, Iran

[41] Shahid Beheshti Univ Med Sci, Mofid Childrens Hosp, Immunol & Allergy Dept, Tehran, Iran

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2018年 / 141卷 / 04期

基金：

美国国家科学基金会;

关键词：

Combined immunodeficiencies; next-generation DNA sequencing; whole-exome sequencing; targeted gene panel sequencing; MOLECULAR DIAGNOSIS; T-CELLS; DISEASES; UPDATE; IRAN; PREVALENCE; DISORDERS; FEATURES; CRITERIA; REGISTRY;

D O I：

10.1016/j.jaci.2017.06.049

中图分类号：

R392 [医学免疫学];

学科分类号：

100108 [医学免疫学];

摘要：

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.

引用

页码：1450 / 1458

页数：9

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