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Journals / Sağlık Bilimlerinde İleri Araştırmalar Dergisi / 2022 / Volume: 5 Issue: 3

GENETIC AND CLINICAL PROFILING OF MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASE PATIENTS; SINGLECENTER EXPERIENCE

MİKOBAKTERİYEL HASTALIKLARA MENDEL DUYARLILIĞI HASTALARININ GENETİK VE KLİNİK PROFİLİ; TEK MERKEZ DENEYİMİ

Serdar Nepesov(Department of Pediatric Allergy and Immunology, Istanbul Medipol University)0000-0002-4551-5433
Sinem Fırtına(Department of Bioinformatics and Genetics, Faculty of Engineering and Natural Sciences, Istinye University)0000-0002-3370-8545
Deniz Aygün(Department of Infectious Diseases, Allergy and Clinical Immunology, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa)0000-0002-7830-7155
Begüm Işıkgil(ISTINYE UNIVERSITY, INSTITUTE OF HEALTH SCIENCES, DEPARTMENT OF MEDICAL BIOLOGY AND GENETICS (INTERDISCIPLINARY) (DISTANT EDUCATION), MEDICAL BIOLOGY AND GENETICS (MASTER) (WITH THESIS))0000-0002-7541-4596
Yıldız Camcıoğlu(Department of Infectious Diseases, Allergy and Clinical Immunology, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa)0000-0002-4796-6828
Ayça Kıykım(Department of Infectious Diseases, Allergy and Clinical Immunology, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa,)0000-0001-5821-3963
Esra Özek(Istanbul University, Istanbul Faculty of Medicine, Department of Pediatric Allergy and Immunology)0000-0003-3712-2522
Yasemin Kendir Demirkol(Department of Pediatric Genetics, Umraniye Teaching and Research Hospital, University of Health Sciences)0000-0001-8016-5224
Akif Ayaz(Department of Medical Genetics, Istanbul Medipol University)0000-0001-6930-7148
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Publication Date
2022-11-16
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

The deficiency of IFN-mediated immunity genes plays a crucial role in the pathogenesis of MSMD and must be considered in pediatric patients with BCGitis.

📌 3 Key Takeaways

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Objective & Hypothesis:Objective: Mendelian susceptibility to mycobacterial disease (MSMD) is a subgroup of primary immunodeficiencies which develops with the Bacille Calmette–Guérin (BCG) vaccine or non-tuberculous mycobacterial infections.
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Key Findings & Data:Materials and Methods: Herein, we performed whole-exome sequencing (WES) on 13 patients with MSMD phenotype.
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Conclusion & Impact:The deficiency of IFN-mediated immunity genes plays a crucial role in the pathogenesis of MSMD and must be considered in pediatric patients with BCGitis.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:MSMD · BCGitis · whole exome sequencing

Abstract

Objective: Mendelian susceptibility to mycobacterial disease (MSMD) is a subgroup of primary immunodeficiencies which develops with the Bacille Calmette–Guérin (BCG) vaccine or non-tuberculous mycobacterial infections. The clinical symptoms have a broad spectrum, from localized to disseminated infections. Materials and Methods: Herein, we performed whole-exome sequencing (WES) on 13 patients with MSMD phenotype. All variants were confirmed by Sanger sequencing. The mean age was 8.41 years (min 3 – max 14 years), and the mean age of symptom onset was 4.6 years in our cohort. Results: We found previously identified IFNGR1 (n=1), IFNGR2 (n=1), TYK2 (n=1), IL12RB1 (n=1), and CYBB (n=1) gene variants in nine patients. Our patients mostly suffered from lymphadenitis (61.5%), osteomyelitis (38%), and miliary tuberculosis (31%). All patients except one had had the BCG vaccination. Two patients developed BCGitis after vaccination. Three patients suffered from disseminated BCG infection (BCGosis). Conclusion: Our findings show the importance of molecular diagnosis in patients with severe infections as an approach for understanding the genetic basis of infectious diseases and deciding on treatment options. The deficiency of IFN-mediated immunity genes plays a crucial role in the pathogenesis of MSMD and must be considered in pediatric patients with BCGitis.

Özet

Amaç: Mikobakteriyel hastalığa (MSMD) Mendel duyarlılığı, Bacille Calmette-Guérin (BCG) aşısı veya tüberküloz dışı mikobakteriyel enfeksiyonlarla gelişen primer immün yetmezliklerin bir alt grubudur. Klinik semptomlar, lokalize enfeksiyondan yayılmış enfeksiyona kadar geniş bir spektruma sahiptir. Gereç ve Yöntem: Bu çalışmada; MSMD fenotipli 13 hastada tüm ekzom dizileme (WES) yaptık. Tüm varyantlar Sanger dizileme ile doğrulandı. Bizim kohortumuzda ortalama yaş 8.41 yıl (en az 3 – en fazla 14 yıl) ve ortalama semptom başlangıç yaşı 4.6 idi. Bulgular: Dokuz hastada; IFNGR1 (n=2), IFNGR2 (n=1), TYK2 (n=1), IL12RB1 (n=1) ve CYBB (n=1) gen varyantları bulduk. Hastalarımızda en çok lenfadenit (%61,5), osteomiyelit (%38) ve miliyer tüberküloz (%31) mevcuttu. Biri hariç tüm hastalara BCG aşısı yapıldı. İki hastada aşılamadan sonra BCGitis gelişti. Üç hasta, yayılmış BCG enfeksiyonundan (BCGosis) muzdaripti. Sonuç: Bulgularımız, enfeksiyon hastalıklarının genetik temelinin anlaşılmasında ve tedavi seçeneklerine karar verilmesinde bir yaklaşım olarak ağır enfeksiyonlu hastalarda moleküler tanının önemini göstermektedir. IFN aracılı bağışıklık genlerinin eksikliği, MSMD’nin patogenezinde çok önemli bir rol oynar ve BCGitis’li pediatrik hastalarda düşünülmelidir.

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Cite This Article

Nepesov, S., Fırtına, S., Aygün, D., Işıkgil, B., Camcıoğlu, Y., Kıykım, A., Özek, E., Demirkol, Y. K., Ayaz, A. (2022). GENETIC AND CLINICAL PROFILING OF MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASE PATIENTS; SINGLECENTER EXPERIENCE. Sağlık Bilimlerinde İleri Araştırmalar Dergisi, Volume: 5 Issue: 3. https://doi.org/10.26650/JARHS2022-1119899

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