ArticleJCI insight2019
NK cell defects in X-linked pigmentary reticulate disorder.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
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- The emerging role of SARS-CoV-2 nonstructural protein 1 (nsp1) in epigenetic regulation of host gene expression.FEMS microbiology reviews · 2024Review
- Variable Syndromic Immunodeficiency in Patients with Biallelic PRIM1 Mutations.Journal of clinical immunology · 2024Article
- Update on ocular manifestations of the main monogenic and polygenic autoinflammatory diseases.Frontiers in ophthalmology · 2024Review
- Unwinding the Role of the CMG Helicase in Inborn Errors of Immunity.Journal of clinical immunology · 2023Article
- Human natural killer cells: Form, function, and development.The Journal of allergy and clinical immunology · 2023Review
- Article
- Partial loss-of-function mutations in GINS4 lead to NK cell deficiency with neutropenia.JCI insight · 2022Article
- X-linked reticulate pigmentary disorder in a 4-year-old boy.Postepy dermatologii i alergologii · 2022Article
- Editorial: Pattern-recognition receptors: Genetics, immunity, pathology.Frontiers in cellular and infection microbiology · 2022Article
- Molecular diagnosis of childhood immune dysregulation, polyendocrinopathy, and enteropathy, and implications for clinical management.The Journal of allergy and clinical immunology · 2022Article
- MCM complex members MCM3 and MCM7 are associated with a phenotypic spectrum from Meier-Gorlin syndrome to lipodystrophy and adrenal insufficiency.European journal of human genetics : EJHG · 2021Article
- Immune Dysfunction in Mendelian Disorders of POLA1 Deficiency.Journal of clinical immunology · 2021Review
- Congenital Diseases of DNA Replication: Clinical Phenotypes and Molecular Mechanisms.International journal of molecular sciences · 2021Review
- JAK Inhibition in a Patient with X-Linked Reticulate Pigmentary Disorder.Journal of clinical immunology · 2021Article
Corrections and comments
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Authors and funding
17 authors at 8 institutions in 3 countries.
Funding
Abstract
X-linked reticulate pigmentary disorder (XLPDR, Mendelian Inheritance in Man #301220) is a rare syndrome characterized by recurrent infections and sterile multiorgan inflammation. The syndrome is caused by an intronic mutation in POLA1, the gene encoding the catalytic subunit of DNA polymerase-α (Pol-α), which is responsible for Okazaki fragment synthesis during DNA replication. Reduced POLA1 expression in this condition triggers spontaneous type I interferon expression, which can be linked to the autoinflammatory manifestations of the disease. However, the history of recurrent infections in this syndrome is as yet unexplained. Here we report that patients with XLPDR have reduced NK cell cytotoxic activity and decreased numbers of NK cells, particularly differentiated, stage V, cells (CD3-CD56dim). This phenotype is reminiscent of hypomorphic mutations in MCM4, which encodes a component of the minichromosome maintenance (MCM) helicase complex that is functionally linked to Pol-α during the DNA replication process. We find that POLA1 deficiency leads to MCM4 depletion and that both can impair NK cell natural cytotoxicity and show that this is due to a defect in lytic granule polarization. Altogether, our study provides mechanistic connections between Pol-α and the MCM complex and demonstrates their relevance in NK cell function.
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