ArticleHuman molecular genetics2013
Haploinsufficiency at the human IFNGR2 locus contributes to mycobacterial disease.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
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Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 64 citations in OpenAlex.
- Genetic, immunologic, and clinical features of 830 patients with Mendelian susceptibility to mycobacterial diseases (MSMD): A systematic review.The Journal of allergy and clinical immunology · 2024Pooled it
- An Updated Review on MSMD Research Globally and A Literature Review on the Molecular Findings, Clinical Manifestations, and Treatment Approaches in China.Frontiers in immunology · 2022Pooled it
- Mendelian susceptibility to mycobacterial disease: IFN-γ-driven immunity collapse underlies heterogeneous infections.Frontiers in immunology · 2026Review
- Incomplete penetrance in inborn errors of immunity: A skeleton in the closet-The sequel.Journal of human immunity · 2025Review
- At-Risk Genomic Findings for Pediatric-Onset Disorders From Genome Sequencing vs Medically Actionable Gene Panel in Proactive Screening of Newborns and Children.JAMA network open · 2023Article
- Severe COVID-19 represents an undiagnosed primary immunodeficiency in a high proportion of infected individuals.Clinical & translational immunology · 2022Review
- A 2-Gene Signature Related to Interferon-Gamma Predicts Prognosis and Responsiveness to Immune Checkpoint Blockade of Glioma.Frontiers in medicine · 2022Article
- Mitochondrial respiration contributes to the interferon gamma response in antigen-presenting cells.eLife · 2021Article
- Phenotypic and immune functional profiling of patients with suspected Mendelian Susceptibility to Mycobacterial Disease in South Africa.BMC immunology · 2021Article
- Cellular and molecular mechanisms breaking immune tolerance in inborn errors of immunity.Cellular & molecular immunology · 2021Review
- Interferon-Driven Immune Dysregulation in Down Syndrome: A Review of the Evidence.Journal of inflammation research · 2021Review
- TREC and KREC profiling as a representative of thymus and bone marrow output in patients with various inborn errors of immunity.Clinical and experimental immunology · 2020Article
- Three Copies of Four Interferon Receptor Genes Underlie a Mild Type I Interferonopathy in Down Syndrome.Journal of clinical immunology · 2020Article
- Mendelian susceptibility to mycobacterial disease: recent discoveries.Human genetics · 2020Review
- Inherited human IFN-γ deficiency underlies mycobacterial disease.The Journal of clinical investigation · 2020Article
- Incomplete penetrance in primary immunodeficiency: a skeleton in the closet.Human genetics · 2020Review
- Patient iPSC-Derived Macrophages to Study Inborn Errors of the IFN-γ Responsive Pathway.Cells · 2020Article
- Primary immunodeficiency diseases in a tuberculosis endemic region: challenges and opportunities.Genes and immunity · 2019Review
- A Novel Splice Site Mutation inFrontiers in immunology · 2019Article
- A purely quantitative form of partial recessive IFN-γR2 deficiency caused by mutations of the initiation or second codon.Human molecular genetics · 2018Article
Corrections and comments
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Authors and funding
25 authors at 1 institution in 1 country.
Funding
Abstract
Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare syndrome, the known genetic etiologies of which impair the production of, or the response to interferon-gamma (IFN-γ). We report here a patient (P1) with MSMD whose cells display mildly impaired responses to IFN-γ, at levels, however, similar to those from MSMD patients with autosomal recessive (AR) partial IFN-γR2 or STAT1 deficiency. Whole-exome sequencing (WES) and Sanger sequencing revealed only one candidate variation for both MSMD-causing and IFN-γ-related genes. P1 carried a heterozygous frame-shift IFNGR2 mutation inherited from her father. We show that the mutant allele is intrinsically loss-of-function and not dominant-negative, suggesting haploinsufficiency at the IFNGR2 locus. We also show that Epstein-Barr virus transformed B lymphocyte cells from 10 heterozygous relatives of patients with AR complete IFN-γR2 deficiency respond poorly to IFN-γ, in some cases as poorly as the cells of P1. Naive CD4(+) T cells and memory IL-4-producing T cells from these individuals also responded poorly to IFN-γ, whereas monocytes and monocyte-derived macrophages (MDMs) did not. This is consistent with the lower levels of expression of IFN-γR2 in lymphoid than in myeloid cells. Overall, MSMD in this patient is probably due to autosomal dominant (AD) IFN-γR2 deficiency, resulting from haploinsufficiency, at least in lymphoid cells. The clinical penetrance of AD IFN-γR2 deficiency is incomplete, possibly due, at least partly, to the variability of cellular responses to IFN-γ in these individuals.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.