Challenges of Diagnosing Mendelian Susceptibility to Mycobacterial Diseases in South Africa
Abstract
:1. Introduction
2. Inborn Errors of Immunity in South Africa
2.1. Susceptibility to Mycobacterial Disease
2.1.1. Age/Sex Influence (the Wonder Years)
2.1.2. BCG-Vaccine Strategy in TB-Endemic Countries
3. Mendelian Susceptibility to Mycobacterial Diseases
3.1. Genes Involved in MSMD
3.2. Clinical Features and Diagnosis
3.2.1. Consanguinity
3.2.2. Effectiveness of BCG Vaccinations
3.2.3. Inheritance of Maternal Immunity
3.2.4. Challenges of Diagnosing MSMD in an Endemic-TB Setting
3.3. Genetic Approaches to Molecular Diagnosis
3.3.1. NGS and Variants of Unknown Significance (VUS)
3.3.2. Under-Representation in the Human Reference Genome
3.3.3. Lack of Transcriptomics as a Diagnostic Tool
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene | MSMD-Causing Mutation Effect |
---|---|
IL12RB1 | Impaired IFN-γ production |
IL12RB2 | Impaired IFN-γ production |
IL12B | Impaired IFN-γ production |
IFNGR1 | Impaired antimicrobial, antiviral, and anti-tumour responses, impaired cellular response to IFN-γ |
IFNGR2 | Impaired antimicrobial, antiviral, and anti-tumour responses, impaired cellular response to IFN-γ |
STAT1 | Defective type I and type II IFN responses |
CYBB | Oxidative burst defects in macrophages |
IRF8 | Loss of myeloid dendritic cells |
TYK2 | Dysregulation of essential signalling for Type I and Type II cytokines |
ISG15 | Impaired IFN-γ production |
RORC | Disruption of IL-27/IFN-γ immunity |
NEMO | Impaired T-cell response and CD40-dependent production of IL-12 |
SPPL2A | Dysfunction of antigen-presenting cells |
JAK1 | Dysfunctional INF-α, IL-6/10, and IL-12 signalling |
IL23R | Dysfunction in the receptor of Type I and Type II cytokines |
TBX21 | Th1 cell-specific transcription factor that functions as a regulator of IFN-γ expression |
ZNFX1 | Can initiate IFN expression following exposure to viruses |
PDCD1 | Immune-inhibitory receptor expressed in activated T cells |
IFNG | Codes for IFN-γ used for communication between cells to trigger the protective defences of the immune system that help eradicate pathogens |
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Scholtz, D.; Jooste, T.; Möller, M.; van Coller, A.; Kinnear, C.; Glanzmann, B. Challenges of Diagnosing Mendelian Susceptibility to Mycobacterial Diseases in South Africa. Int. J. Mol. Sci. 2023, 24, 12119. https://doi.org/10.3390/ijms241512119
Scholtz D, Jooste T, Möller M, van Coller A, Kinnear C, Glanzmann B. Challenges of Diagnosing Mendelian Susceptibility to Mycobacterial Diseases in South Africa. International Journal of Molecular Sciences. 2023; 24(15):12119. https://doi.org/10.3390/ijms241512119
Chicago/Turabian StyleScholtz, Denise, Tracey Jooste, Marlo Möller, Ansia van Coller, Craig Kinnear, and Brigitte Glanzmann. 2023. "Challenges of Diagnosing Mendelian Susceptibility to Mycobacterial Diseases in South Africa" International Journal of Molecular Sciences 24, no. 15: 12119. https://doi.org/10.3390/ijms241512119