Identification of a novel variant of <i>FOXP3</i> resulting in severe immune dysregulation, polyendocrinopathy, enteropathy, X‐linked syndrome highlights potential pitfalls of molecular testing

Kirchner, Allison; Sanchez, Isabelle M.; Zalan, Alice; Bhat, Gifty; Bain, Michelle

doi:10.1111/pde.14936

Cited by 2 publications

(1 citation statement)

References 5 publications

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“…However, several studies have shown that the FOXP3 gene is not essential for the establishment of the Treg cell lineage, but rather for its suppressive effector functions, as it controls the expression of different regulatory molecules such as TIGIT, CTLA-4, and the suppression of the IL-2 gene and different effector T-cell cytokines ( 59 – 61 ). Reported mutations causing IPEX are null or nonsense variants and small deletions or insertions in the reading frame ( 62 – 64 ) in the FOXP3 gene that result in a residual expression of the protein, but lacking function. Therefore, Treg cells from these patients are dysfunctional, being unable to inhibit the proliferation and inflammatory functions of effector T cells (Teff) ( 62 , 65 , 66 ).…”

Section: Iei and Treg: The New Kid On The Blockmentioning

confidence: 99%

Treg in inborn errors of immunity: gaps, knowns and future perspectives

Kennedy-Batalla,

Acevedo,

Luo

et al. 2024

Front. Immunol.

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Regulatory T cells (Treg) are essential for immune balance, preventing overreactive responses and autoimmunity. Although traditionally characterized as CD4+CD25+CD127lowFoxP3hi, recent research has revealed diverse Treg subsets such as Tr1, Tr1-like, and CD8 Treg. Treg dysfunction leads to severe autoimmune diseases and immune-mediated inflammatory disorders. Inborn errors of immunity (IEI) are a group of disorders that affect correct functioning of the immune system. IEI include Tregopathies caused by genetic mutations affecting Treg development or function. In addition, Treg dysfunction is also observed in other IEIs, whose underlying mechanisms are largely unknown, thus requiring further research. This review provides a comprehensive overview and discussion of Treg in IEI focused on: A) advances and controversies in the evaluation of Treg extended subphenotypes and function; B) current knowledge and gaps in Treg disturbances in Tregopathies and other IEI including Treg subpopulation changes, genotype-phenotype correlation, Treg changes with disease activity, and available therapies, and C) the potential of Treg cell-based therapies for IEI with immune dysregulation. The aim is to improve both the diagnostic and the therapeutic approaches to IEI when there is involvement of Treg. We performed a non-systematic targeted literature review with a knowledgeable selection of current, high-quality original and review articles on Treg and IEI available since 2003 (with 58% of the articles within the last 6 years) in the PubMed database.

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Section: Iei and Treg: The New Kid On The Blockmentioning

confidence: 99%

Treg in inborn errors of immunity: gaps, knowns and future perspectives

Kennedy-Batalla,

Acevedo,

Luo

et al. 2024

Front. Immunol.

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Anamnestic, clinical, laboratory and molecular genetic characteristics of patients with neonatal diabetes mellitus

Ivanov,

Ditkovskaya,

Maryina

et al. 2024

Pediatr (SPb)

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BACKGROUND: Currently, there is an increase in the incidence of diabetes mellitus throughout the world, including the steadily increasing number of rare, genetically determined forms of diabetes. Of particular interest are monogenic forms, including neonatal diabetes mellitus, which is a rare heterogeneous disease that manifests, as a rule, in the first 6 months of a child’s life, characterized by a severe labile course and a high risk of complications. Neonatal diabetes mellitus is a rare heterogeneous disease that usually manifests itself in the first 6 months of a child’s life, characterized by a severe, labile course and a high risk of complications. Currently, more than 25 genes are known, mutations in which cause both permanent and transient neonatal diabetes mellitus, as well as syndromic variants of this disease, which are of particular interest due to their severity and polymorphic clinical picture. In this regard, timely verification of the diagnosis is of particular importance. AIM: The aim of this study is to increase the efficiency of diagnosis of neonatal diabetes mellitus based on the analysis of anamnestic, clinical, laboratory and molecular genetic characteristics of patients. MATERIALS AND METHODS: 14 patients with transient and permanent neonatal diabetes mellitus were examined. RESULTS: 11 (78.6%) patients had isolated neonatal diabetes, in three of them the disease was verified in the structure of hereditary syndromes (Wolcott–Rallison syndrome, IPEX syndrome and Donohue syndrome). According to molecular genetic analysis, 14 variants were found in the genes ABCC8, KCNJ11, GCK, GATA6, WFS1, CACNA1D, EIF2AK3, FOXP3, PAX4, INSR, IGF1R, three of which were not previously described in the literature. CONCLUSIONS: The clinical heterogeneity identified in patients is determined primarily by the diversity of verified variants in causative genes. New variants in the CACNA1D and IGF1R genes that may be associated with the development of NDM, remain poorly understood and require further research.

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Identification of a novel variant of FOXP3 resulting in severe immune dysregulation, polyendocrinopathy, enteropathy, X‐linked syndrome highlights potential pitfalls of molecular testing

Cited by 2 publications

References 5 publications

Treg in inborn errors of immunity: gaps, knowns and future perspectives

Treg in inborn errors of immunity: gaps, knowns and future perspectives

Anamnestic, clinical, laboratory and molecular genetic characteristics of patients with neonatal diabetes mellitus

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