Trial reportThe Journal of allergy and clinical immunology2020
Combined immunodeficiency caused by a loss-of-function mutation in DNA polymerase delta 1.
Trial report in The Journal of allergy and clinical immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 37 citations in OpenAlex.
- Heterogeneous immune cell composition in patients with combined immunodeficiency.Frontiers in immunology · 2026Article
- Replication stress, microcephalic primordial dwarfism, and compromised immunity in ATRIP deficient patients.The Journal of experimental medicine · 2025Article
- POLD3 haploinsufficiency is linked to non-syndromic sensorineural adult-onset progressive hearing and balance impairments.European journal of human genetics : EJHG · 2025Article
- Human Autosomal Recessive DNA Polymerase Delta 3 Deficiency Presenting as Omenn Syndrome.Journal of clinical immunology · 2023Article
- Prospects of POLD1 in Human Cancers: A Review.Cancers · 2023Review
- Non-canonical binding of the Chaetomium thermophilum PolD4 N-terminal PIP motif to PCNA involves Q-pocket and compact 2-fork plug interactions but no 3The FEBS journal · 2023Article
- Canonical binding ofFrontiers in molecular biosciences · 2023Article
- Article
- Congenital Diseases of DNA Replication: Clinical Phenotypes and Molecular Mechanisms.International journal of molecular sciences · 2021Review
- Sulfamethoxazole-Altered Transcriptomein Green AlgaFrontiers in microbiology · 2021Article
- Anlotinib suppresses MLL-rearranged acute myeloid leukemia cell growth by inhibiting SETD1A/AKT-mediated DNA damage response.American journal of translational research · 2021Article
- CTCF Mediates Replicative Senescence Through POLD1.Frontiers in cell and developmental biology · 2021Article
- POLD1 Deficiency Reveals a Role for POLD1 in DNA Repair and T and B Cell Development.Journal of clinical immunology · 2021Article
- Determinants of neurological syndromes caused by varicella zoster virus (VZV).Journal of neurovirology · 2020Review
- Human inborn errors of immunity to herpes viruses.Current opinion in immunology · 2020Review
- Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee.Journal of clinical immunology · 2020Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMutations affecting DNA polymerases have been implicated in genomic instability and cancer development, but the mechanisms by which they can affect the immune system remain largely unexplored.
objectiveWe sought to establish the role of DNA polymerase δ1 catalytic subunit (POLD1) as the cause of a primary immunodeficiency in an extended kindred.
methodsWe performed whole-exome and targeted gene sequencing, lymphocyte characterization, molecular and functional analyses of the DNA polymerase δ (Polδ) complex, and T- and B-cell antigen receptor repertoire analysis.
resultsWe identified a missense mutation (c. 3178C>T; p.R1060C) in POLD1 in 3 related subjects who presented with recurrent, especially herpetic, infections and T-cell lymphopenia with impaired T-cell but not B-cell proliferation. The mutation destabilizes the Polδ complex, leading to ineffective recruitment of replication factor C to initiate DNA replication. Molecular dynamics simulation revealed that the R1060C mutation disrupts the intramolecular interaction between the POLD1 CysB motif and the catalytic domain and also between POLD1 and the Polδ subunit POLD2. The patients exhibited decreased numbers of naive CD4 and especially CD8 T cells in favor of effector memory subpopulations. This skewing was associated with oligoclonality and restricted T-cell receptor β-chain V-J pairing in CD8
conclusionThese results identify gene defects in POLD1 as a novel cause of T-cell immunodeficiency.
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What OpenQuestion holds
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.