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更新于：2025-05-07

Mendelian susceptibility to mycobacterial disease

孟德尔对分枝杆菌病的易感性

更新于：2025-05-07

基本信息

别名

MSMD - mendelian susceptibility to mycobacterial disease、Mendelian Susceptibility to Mycobacterial Diseases、Mendelian susceptibility to mycobacterial disease

+ [3]

简介

A rare inherited disorder typically presenting in childhood characterized by a susceptibly to infection (local and disseminated), particularly from mycobacteria. This disorder has been associated with mutations in several genes including: IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, IRF8, ISG15, IKBKG, CYBB.

关联

项与孟德尔对分枝杆菌病的易感性相关的药物

CD3/CD19 negative allogeneic hematopoietic stem cells(University of Pittsburgh)

靶点

CD19 x CD3

作用机制

CD19调节剂 [+2]

在研机构

University of Pittsburgh

原研机构

University of Pittsburgh

在研适应症

普通可变性免疫缺陷 [+7]

非在研适应症-

最高研发阶段临床1/2期

首次获批国家/地区-

首次获批日期1800-01-20

项与孟德尔对分枝杆菌病的易感性相关的临床试验

NCT04256395

/ CompletedN/AIIT

Registry Study on the Efficacy of a Self-test and Self-alert Applet in Detecting Susceptible Infection of COVID-19 --a Population Based Mobile Internet Survey

The "COVID-19 infection self-test and alert system" (hereinafter referred to as "COVID-19 self-test applet") jointly developed by Beijing Tsinghua Changgung Hospital, Institute for precision medicine, artificial intelligence of Tsinghua University was launched on February 1，2020. Residents , according to their actual healthy situation, after answering questions online, the system will conduct intelligent analysis, make disease risk assessment and give healthcare and medical guidance. Based on the Internet population survey, and referring to the diagnosis and screening standards of the National Health Commission of the People's Republic of China, investigators carried out the mobile applet of Internet survey and registry study for the Internet accessible identifiable population, so as to screen the suspected population and guide the medical treatment.

开始日期2020-02-01

申办/合作机构

中国医师协会

NCT01852370

/ Enrolling by invitation临床1/2期IIT

Bilateral Orthotopic Lung Transplant in Tandem with CD3+ and CD19+ Cell Depleted Bone Marrow Transplant from Partially HLA-Matched Cadaveric Donors

The purpose of this study is to determine whether bilateral orthotopic lung transplantation (BOLT) followed by cadaveric partially-matched hematopoietic stem cell transplantation (HSCT) is safe and effective for patients aged 5-45 years with primary immunodeficiency (PID) and end-stage lung disease.

开始日期2013-06-20

申办/合作机构

University of Pittsburgh

100 项与孟德尔对分枝杆菌病的易感性相关的临床结果

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100 项与孟德尔对分枝杆菌病的易感性相关的转化医学

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0 项与孟德尔对分枝杆菌病的易感性相关的专利（医药）

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项与孟德尔对分枝杆菌病的易感性相关的文献（医药）

2025-12-01·Journal of Clinical Immunology

First Brazilian Case Report of Unrelated Patients with Identical ISG15 Mutation

Article

作者: Napoleao, Sarah Maria da Silva ; de Barros Dorna, Mayra ; Franca, Tabata Takahashi ; Salgado, Ranieri Coelho ; Ferreira, Janaira Fernandes Severo ; de Moura, Thais Costa Lima ; Gomes, Lillian Nunes ; Condino-Neto, Antonio ; Barreiros, Lucila Akune

BACKGROUNDISG15 deficiency is a mixed syndrome of Mendelian susceptibility to mycobacterial infections (MSMD), a rare inherited condition characterized primarily by recurrent infections from low-virulence mycobacteria and monogenic type I interferonopathy.OBJECTIVETo characterize the laboratory and molecular features of two patients from different families affected by the same ISG15 variant.METHODSWe began with clinical characterization and investigation, assessed IL-12/IFN-γ production, performed genetic characterization through WES and Sanger sequencing, conducted an in silico molecular analysis of the genetic ISG15 variant's protein impact, and utilized RNAseq for transcriptome analysis to understand pathway impacts on ISG15-deficient subjects from unrelated families.RESULTSA mutation in the ISG15 gene was identified, affecting two patients treated in different hospitals and cities in Brazil (Fortaleza and Sao Paulo), who are also members of unrelated families. Both patients showed low IFN-γ production when stimulated with BCG or BCG + IL-12. ISG15 deficiency presented with two distinct clinical phenotypes: infectious and neurological. It was identified that both patients are homozygous for the variant (c.83 T > A). Furthermore, it was observed that the mutant protein p.L28Q results in an unstable protein with increased flexibility (ΔΔG: -2.400 kcal/mol). Transcriptome analysis revealed 1321 differentially expressed genes, with significant upregulation in interferon pathways, showing higher expression in patients compared to controls.CONCLUSIONThis study describes the first reported cases in Brazil of two unrelated patients with the same ISG15 mutation c.83 T > A, exhibiting infectious features such as mycobacterial infections and systemic candidiasis, neurological findings, and skin lesions, without adverse reactions to the BCG vaccine.CLINICAL IMPLICATIONSReporting ISG15 gene mutations in Brazilian patients enhances understanding of genetic susceptibilities, guiding effective diagnostics and treatment. Identifying high-risk individuals aids clinical practices, genetic counseling, and influences public health policies. We have identified the first case in Brazil of the same ISG15 variant c.83 T > A that was identified in two unrelated patients with distinct clinical phenotypes, infectious and neurological.

2023-07-29·BMC pediatrics

A rare mutation causing autosomal dominant STAT1 deficiency in a South African multiplex kindred with disseminated BCG infection.

Article

作者: Wieselthaler, Nicole ; Lau, Yu Lung ; Chan, Koon Wing ; Eley, Brian ; Greybe, Leonore ; le Roux, David M ; Leung, Daniel

BACKGROUNDAutosomal dominant signal transducer and activator of transcription 1 (STAT1) deficiency, part of the Mendelian susceptibility to mycobacterial disease (MSMD) group, frequently causes disseminated Bacillus Calmette-Guérin (BCG) infections, but has not been reported from Sub-Saharan Africa (SSA) where routine birth BCG vaccination is practiced.CASE PRESENTATIONTwo half-siblings presented five years apart, with multifocal osteomyelitis as the dominant feature of disseminated BCG, which was successfully treated with antimycobacterial therapy. Whole exome sequencing demonstrated a novel heterozygous substitution in the splice site between intron 13 and exon 14 of the STAT1 gene, NM_007315: c.1128-1G>A, in the proband and his mother and was later confirmed in his half-brother.CONCLUSIONSChildren with BCG vaccine complications in SSA should be referred for further investigation and particular consideration of MSMD.

2023-07-28·International journal of molecular sciences

Challenges of Diagnosing Mendelian Susceptibility to Mycobacterial Diseases in South Africa.

Review

作者: Scholtz, Denise ; Jooste, Tracey ; Glanzmann, Brigitte ; Kinnear, Craig ; van Coller, Ansia ; Möller, Marlo

Inborn errors of immunity (IEI) are genetic disorders with extensive clinical presentations. They can range from increased susceptibility to infections to significant immune dysregulation that results in immune impairment. While IEI cases are individually rare, they collectively represent a significant burden of disease, especially in developing countries such as South Africa, where infectious diseases like tuberculosis (TB) are endemic. This is particularly alarming considering that certain high penetrance mutations that cause IEI, such as Mendelian Susceptibility to Mycobacterial Disease (MSMD), put individuals at higher risk for developing TB and other mycobacterial diseases. MSMD patients in South Africa often present with different clinical phenotypes than those from the developed world, therefore complicating the identification of disease-associated variants in this setting with a high burden of infectious diseases. The lack of available data, limited resources, as well as variability in clinical phenotype are the reasons many MSMD cases remain undetected or misdiagnosed. This article highlights the challenges in diagnosing MSMD in South Africa and proposes the use of transcriptomic analysis as a means of potentially identifying dysregulated pathways in affected African populations.

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