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Clinical, Immunologic, and Genetic Spectrum of 696 Patients With Combined Immunodeficiency Publisher Pubmed



Abolhassani H1, 2 ; Chou J3 ; Bainter W3 ; Platt CD3 ; Tavassoli M4 ; Momen T4 ; Tavakol M5 ; Eslamian MH6 ; Gharagozlou M7 ; Movahedi M7 ; Ghadami M8 ; Hamidieh AA9 ; Azizi G10 ; Yazdani R1, 11 Show All Authors
Authors
  1. Abolhassani H1, 2
  2. Chou J3
  3. Bainter W3
  4. Platt CD3
  5. Tavassoli M4
  6. Momen T4
  7. Tavakol M5
  8. Eslamian MH6
  9. Gharagozlou M7
  10. Movahedi M7
  11. Ghadami M8
  12. Hamidieh AA9
  13. Azizi G10
  14. Yazdani R1, 11
  15. Afarideh M1
  16. Ghajar A1
  17. Havaei A1
  18. Chavoshzadeh Z12
  19. Mahdaviani SA13
  20. Cheraghi T14
  21. Behniafard N15
  22. Amin R16
  23. Aleyasin S16
  24. Faridhosseini R17
  25. Jabbariazad F17
  26. Nabavi M18
  27. Bemanian MH18
  28. Arshi S18
  29. Molatefi R18, 19
  30. Sherkat R20
  31. Mansouri M37
  32. Mesdaghi M12
  33. Babaie D12
  34. Mohammadzadeh I21
  35. Ghaffari J22
  36. Shafiei A23
  37. Kalantari N24
  38. Ahanchian H17
  39. Khoshkhui M17
  40. Soheili H25
  41. Dabbaghzadeh A21
  42. Shirkani A26
  43. Nasiri Kalmarzi R27
  44. Mortazavi SH28
  45. Tafaroji J29
  46. Khalili A30
  47. Mohammadi J31
  48. Negahdari B32
  49. Joghataei MT33
  50. Alramadi BK34
  51. Picard C35
  52. Parvaneh N1
  53. Rezaei N1, 36
  54. Chatila TA3
  55. Massaad MJ3
  56. Keles S3
  57. Hammarstrom L2
  58. Geha RS3
  59. Aghamohammadi A1, 36

Source: Journal of Allergy and Clinical Immunology Published: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. 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
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