Demographic, clinical, immunological, and molecular features of iranian national cohort of patients with defect in DCLRE1C gene.
Artemis
DCLRE1C
HSCT
Inborn errors of immunity
Primary immunodeficiency
Severe combined immunodeficiency
Journal
Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology
ISSN: 1710-1484
Titre abrégé: Allergy Asthma Clin Immunol
Pays: England
ID NLM: 101244313
Informations de publication
Date de publication:
21 Feb 2023
21 Feb 2023
Historique:
received:
11
10
2022
accepted:
05
02
2023
entrez:
22
2
2023
pubmed:
23
2
2023
medline:
23
2
2023
Statut:
epublish
Résumé
DCLRE1C gene mutation leads to Artemis deficiency, a severe form of combined immunodeficiency (SCID). Impaired DNA repair and block in early adaptive immunity maturation results in T-B-NK+ immunodeficiency associated with radiosensitivity. Recurrent infections early in life are the main characteristic of Artemis patients. Among 5373 registered patients, 9 Iranian patients (33.3% female) with confirmed DCLRE1C mutation were identified since 1999-2022. The demographic, clinical, immunological and genetic features were collected through retrospective investigation of medical records and using next generation sequencing. Seven patients were born in a consanguineous family (77.8%). The median age of onset was 6.0 (5.0-17.0) months. Severe combined immunodeficiency (SCID) was clinically detected at a median (IQR) age of 7.0 (6.0-20.5) months, following a median diagnostic delay of 2.0 (1.0-3.5) months The most typical first presentation was pneumonia (44.4%) and otitis media (3.33%), followed by BCG lymphadenitis (22.2%) and gastroenteritis (11.1%). The most prevalent manifestations were respiratory tract infections (including otitis media) (66.6%) and chronic diarrhea (66.6%). In addition, juvenile idiopathic arthritis (P5) and celiac disease and idiopathic thrombocytopenic purpura (P9) as autoimmune disorders were reported in 2 patients. All patients had reduced B CD19+ and CD4+ cell counts. IgA deficiency occurred in 77.8% of individuals. Recurrent infections particulary respiratory tract infection and chronic diarrhea during the first months of life in patients born to consanguineous parents should raise the suspicion for inborn errors of immunity, even in the presence of normal growth and development.
Sections du résumé
BACKGROUND
BACKGROUND
DCLRE1C gene mutation leads to Artemis deficiency, a severe form of combined immunodeficiency (SCID). Impaired DNA repair and block in early adaptive immunity maturation results in T-B-NK+ immunodeficiency associated with radiosensitivity. Recurrent infections early in life are the main characteristic of Artemis patients.
METHOD
METHODS
Among 5373 registered patients, 9 Iranian patients (33.3% female) with confirmed DCLRE1C mutation were identified since 1999-2022. The demographic, clinical, immunological and genetic features were collected through retrospective investigation of medical records and using next generation sequencing.
RESULTS
RESULTS
Seven patients were born in a consanguineous family (77.8%). The median age of onset was 6.0 (5.0-17.0) months. Severe combined immunodeficiency (SCID) was clinically detected at a median (IQR) age of 7.0 (6.0-20.5) months, following a median diagnostic delay of 2.0 (1.0-3.5) months The most typical first presentation was pneumonia (44.4%) and otitis media (3.33%), followed by BCG lymphadenitis (22.2%) and gastroenteritis (11.1%). The most prevalent manifestations were respiratory tract infections (including otitis media) (66.6%) and chronic diarrhea (66.6%). In addition, juvenile idiopathic arthritis (P5) and celiac disease and idiopathic thrombocytopenic purpura (P9) as autoimmune disorders were reported in 2 patients. All patients had reduced B CD19+ and CD4+ cell counts. IgA deficiency occurred in 77.8% of individuals.
CONCLUSION
CONCLUSIONS
Recurrent infections particulary respiratory tract infection and chronic diarrhea during the first months of life in patients born to consanguineous parents should raise the suspicion for inborn errors of immunity, even in the presence of normal growth and development.
Identifiants
pubmed: 36810129
doi: 10.1186/s13223-023-00768-5
pii: 10.1186/s13223-023-00768-5
pmc: PMC9942309
doi:
Types de publication
Journal Article
Langues
eng
Pagination
13Informations de copyright
© 2023. The Author(s).
Références
Immunol Lett. 2019 Dec;216:70-78
pubmed: 31589898
Front Pediatr. 2019 Sep 18;7:373
pubmed: 31620409
Front Immunol. 2021 Feb 25;12:648951
pubmed: 33717203
Nucleic Acids Res. 2022 Feb 28;50(4):2096-2110
pubmed: 35150269
J Allergy Clin Immunol. 2015 Jul;136(1):140-150.e7
pubmed: 25917813
Clin Immunol. 2013 Dec;149(3):464-74
pubmed: 24230999
J Clin Immunol. 2018 Aug;38(6):727-732
pubmed: 30105620
J Allergy Clin Immunol. 2018 Apr;141(4):1450-1458
pubmed: 28916186
Immunobiology. 2020 May;225(3):151961
pubmed: 32517885
J Clin Immunol. 2006 Nov;26(6):519-32
pubmed: 17024564
Ann Allergy Asthma Immunol. 2022 Jan;128(1):12-18
pubmed: 34628007
J Clin Immunol. 2021 Aug;41(6):1339-1351
pubmed: 34052995
Reprod Sci. 2021 Dec;28(12):3303-3315
pubmed: 34101149
Pediatr Allergy Immunol. 2022 Jun;33(6):e13820
pubmed: 35754136
J Clin Immunol. 2018 Oct;38(7):816-832
pubmed: 30302726
J Allergy Clin Immunol. 2015 Nov;136(5):1178-85
pubmed: 26055221
Front Immunol. 2020 Jul 09;11:1417
pubmed: 32754152
Clin Immunol. 2020 Apr;213:108366
pubmed: 32092471
Allergol Immunopathol (Madr). 2022 Jan 01;50(1):80-84
pubmed: 34935317
Blood. 2014 Jan 9;123(2):281-9
pubmed: 24144642
Pediatr Transplant. 2012 Aug;16(5):E167-71
pubmed: 21535335
J Allergy Clin Immunol. 2021 Feb;147(2):417-426
pubmed: 33551023
JAMA. 2014 Aug 20;312(7):729-38
pubmed: 25138334
Clin Immunol. 2015 May;158(1):29-34
pubmed: 25762520
J Clin Immunol. 2021 Nov;41(8):1762-1773
pubmed: 34370170
J Allergy Clin Immunol. 2022 May;149(5):1744-1754.e8
pubmed: 34718043
Ann N Y Acad Sci. 2011 Dec;1246:50-63
pubmed: 22236430
Clin Immunol. 2019 Mar;200:16-18
pubmed: 30630113
J Clin Immunol. 2021 Apr;41(3):631-638
pubmed: 33411152
Bone Marrow Transplant. 2001 Apr;27(7):703-9
pubmed: 11360109
Clin Immunol. 2022 Nov;244:109131
pubmed: 36179983
Nucleic Acids Res. 2021 Sep 20;49(16):9310-9326
pubmed: 34387696
Hum Mol Genet. 2015 Dec 20;24(25):7361-72
pubmed: 26476407