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

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 infec...

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Main Authors: Serdar Nepesov, Sinem Fırtına, Fatma Deniz Aygün, Begüm Işıkgil, Yıldız Çamcıoğlu, Ayça Kıykım, Esra Özek Yücel, Yasemin Kendir Demirkol, Akif Ayaz
Format: Article
Language:English
Published: Istanbul University Press 2022-10-01
Series:Sabiad
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Online Access:https://cdn.istanbul.edu.tr/file/JTA6CLJ8T5/BF1AA886F85D407A9903ECFB75289D73
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author Serdar Nepesov
Sinem Fırtına
Fatma Deniz Aygün
Begüm Işıkgil
Yıldız Çamcıoğlu
Ayça Kıykım
Esra Özek Yücel
Yasemin Kendir Demirkol
Akif Ayaz
author_facet Serdar Nepesov
Sinem Fırtına
Fatma Deniz Aygün
Begüm Işıkgil
Yıldız Çamcıoğlu
Ayça Kıykım
Esra Özek Yücel
Yasemin Kendir Demirkol
Akif Ayaz
author_sort Serdar Nepesov
collection DOAJ
description 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.
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publisher Istanbul University Press
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spelling doaj-art-fe587b6bfe3746c4b631e345df6165ac2025-08-20T03:53:07ZengIstanbul University PressSabiad2651-40602022-10-015314014610.26650/JARHS2022-1119899123456GENETIC AND CLINICAL PROFILING OF MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASE PATIENTS; SINGLE CENTER EXPERIENCESerdar Nepesov0https://orcid.org/0000-0002-4551-5433Sinem Fırtına1https://orcid.org/0000-0002-3370-8545Fatma Deniz Aygün2https://orcid.org/0000-0002-7830-7155Begüm Işıkgil3https://orcid.org/0000-0002-7541-4596Yıldız Çamcıoğlu4https://orcid.org/0000-0002-4796-6828Ayça Kıykım5https://orcid.org/0000-0001-5821-3963Esra Özek Yücel6https://orcid.org/0000-0003-3712-2522Yasemin Kendir Demirkol7https://orcid.org/0000-0001-8016-5224Akif Ayaz8https://orcid.org/0000-0001-6930-7148İstanbul Medipol Üniversitesi, Istanbul, Turkiyeİstinye Üniversitesi, Istanbul, Turkiyeİstanbul Üniversitesi-Cerrahpaşa, Istanbul, Turkiyeİstinye Üniversitesi, Istanbul, Turkiyeİstanbul Üniversitesi-Cerrahpaşa, Istanbul, Turkiyeİstanbul Üniversitesi-Cerrahpaşa, Istanbul, Turkiyeİstanbul Üniversitesi, İstanbul, TürkiyeSağlık Bilimleri Üniversitesi, Istanbul, Turkiyeİstanbul Medipol Üniversitesi, Istanbul, TurkiyeObjective: 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.https://cdn.istanbul.edu.tr/file/JTA6CLJ8T5/BF1AA886F85D407A9903ECFB75289D73msmdbcgitiswhole exome sequencing
spellingShingle Serdar Nepesov
Sinem Fırtına
Fatma Deniz Aygün
Begüm Işıkgil
Yıldız Çamcıoğlu
Ayça Kıykım
Esra Özek Yücel
Yasemin Kendir Demirkol
Akif Ayaz
GENETIC AND CLINICAL PROFILING OF MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASE PATIENTS; SINGLE CENTER EXPERIENCE
Sabiad
msmd
bcgitis
whole exome sequencing
title GENETIC AND CLINICAL PROFILING OF MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASE PATIENTS; SINGLE CENTER EXPERIENCE
title_full GENETIC AND CLINICAL PROFILING OF MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASE PATIENTS; SINGLE CENTER EXPERIENCE
title_fullStr GENETIC AND CLINICAL PROFILING OF MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASE PATIENTS; SINGLE CENTER EXPERIENCE
title_full_unstemmed GENETIC AND CLINICAL PROFILING OF MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASE PATIENTS; SINGLE CENTER EXPERIENCE
title_short GENETIC AND CLINICAL PROFILING OF MENDELIAN SUSCEPTIBILITY TO MYCOBACTERIAL DISEASE PATIENTS; SINGLE CENTER EXPERIENCE
title_sort genetic and clinical profiling of mendelian susceptibility to mycobacterial disease patients single center experience
topic msmd
bcgitis
whole exome sequencing
url https://cdn.istanbul.edu.tr/file/JTA6CLJ8T5/BF1AA886F85D407A9903ECFB75289D73
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