Whole-exome sequencing to identify undiagnosed primary immunodeficiency disorders in children with community-acquired sepsis, admitted in the pediatric intensive care unit
© 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd..
BACKGROUND: Whole-exome sequencing (WES) provides a powerful diagnostic tool for identifying primary immunodeficiency diseases (PIDs). This study explores the utility of this approach in uncovering previously undiagnosed PIDs in children with community-acquired sepsis (CAS), with a medical history of recurrent infections or a family history of PIDs.
METHODS: We performed WES on DNA samples extracted from the blood of the 34 enrolled patients, followed by bioinformatic analysis for variant calling, annotation, and prioritization. We also performed a segregation analysis in available family members to confirm the inheritance patterns and assessed the potential impact of the identified variants on protein function.
RESULTS: From 34 patients enrolled in the study, 29 patients (85%) with previously undiagnosed genetic diseases, including 28 patients with PIDs and one patient with interstitial lung and liver disease, were identified. We identified two patients with severe combined immunodeficiency (SCID), patients with combined immunodeficiency (CID), six patients with combined immunodeficiency with syndromic features (CID-SF), four patients with defects in intrinsic and innate immunity, four patients with congenital defects of phagocyte function (CPDF), and six patients with the disease of immune dysregulation. Autoinflammatory disorders and predominantly antibody deficiency were diagnosed in one patient each.
CONCLUSION: Our findings demonstrate the potential of WES in identifying undiagnosed PIDs in children with CAS. Implementing WES in the clinical evaluation of CAS patients with a warning sign for PIDs can aid in their timely diagnosis and potentially lead to improved patient care.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:34 |
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| Enthalten in: |
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology - 34(2023), 12 vom: 26. Dez., Seite e14066 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rayzan, Elham [VerfasserIn] |
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| Links: |
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| Themen: |
Combined immunodeficiency |
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| Anmerkungen: |
Date Completed 27.12.2023 Date Revised 27.12.2023 published: Print Citation Status MEDLINE |
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| doi: |
10.1111/pai.14066 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366367757 |
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| 520 | |a © 2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. | ||
| 520 | |a BACKGROUND: Whole-exome sequencing (WES) provides a powerful diagnostic tool for identifying primary immunodeficiency diseases (PIDs). This study explores the utility of this approach in uncovering previously undiagnosed PIDs in children with community-acquired sepsis (CAS), with a medical history of recurrent infections or a family history of PIDs | ||
| 520 | |a METHODS: We performed WES on DNA samples extracted from the blood of the 34 enrolled patients, followed by bioinformatic analysis for variant calling, annotation, and prioritization. We also performed a segregation analysis in available family members to confirm the inheritance patterns and assessed the potential impact of the identified variants on protein function | ||
| 520 | |a RESULTS: From 34 patients enrolled in the study, 29 patients (85%) with previously undiagnosed genetic diseases, including 28 patients with PIDs and one patient with interstitial lung and liver disease, were identified. We identified two patients with severe combined immunodeficiency (SCID), patients with combined immunodeficiency (CID), six patients with combined immunodeficiency with syndromic features (CID-SF), four patients with defects in intrinsic and innate immunity, four patients with congenital defects of phagocyte function (CPDF), and six patients with the disease of immune dysregulation. Autoinflammatory disorders and predominantly antibody deficiency were diagnosed in one patient each | ||
| 520 | |a CONCLUSION: Our findings demonstrate the potential of WES in identifying undiagnosed PIDs in children with CAS. Implementing WES in the clinical evaluation of CAS patients with a warning sign for PIDs can aid in their timely diagnosis and potentially lead to improved patient care | ||
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| 650 | 4 | |a whole-exome sequencing | |
| 700 | 1 | |a Mirbeyk, Mona |e verfasserin |4 aut | |
| 700 | 1 | |a Pezeshki, Parmida Sadat |e verfasserin |4 aut | |
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| 700 | 1 | |a Sharifzadeh, Meisam |e verfasserin |4 aut | |
| 700 | 1 | |a Tahernia, Leila |e verfasserin |4 aut | |
| 700 | 1 | |a Rezaei, Nima |e verfasserin |4 aut | |
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