ArticleThe Journal of allergy and clinical immunology2015
Functional analysis of naturally occurring DCLRE1C mutations and correlation with the clinical phenotype of ARTEMIS deficiency.
Article in The Journal of allergy and clinical immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 74 citations in OpenAlex.
- Base editing of Artemis mutations ex vivo sheds light on gene therapy for Artemis-deficient SCID.Advanced biotechnology · 2026Article
- Targeted Next-Generation Sequencing in the Molecular Diagnosis of Severe Combined Immunodeficiency.Medicina (Kaunas, Lithuania) · 2025Article
- Targeting Artemis Sensitizes B Cells to Topoisomerase 2 Poisons by Disrupting DNA-PKcs-Dependent Repair.Research square · 2025Article
- Investigating Chromosomal Radiosensitivity in Inborn Errors of Immunity: Insights from DNA Repair Disorders and Beyond.Journal of clinical immunology · 2025Article
- Coexistence of a Leaky SCID Phenotype With Hyperphenylalaninemia in an Adult Case.Case reports in immunology · 2025Article
- RAG recombinase expression discriminates the development of natural killer cells.Frontiers in immunology · 2025Article
- Mutational analysis in different genes underlying severe combined immunodeficiency in seven consanguineous Pakistani families.Molecular biology reports · 2024Article
- A Clinical Conundrum with Diagnostic and Therapeutic Challenge: a Tale of Two Disorders in One Case.Journal of clinical immunology · 2023Article
- Correcting inborn errors of immunity: From viral mediated gene addition to gene editing.Seminars in immunology · 2023Review
- Demographic, clinical, immunological, and molecular features of iranian national cohort of patients with defect in DCLRE1C gene.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2023Article
- Artemis inhibition as a therapeutic strategy for acute lymphoblastic leukemia.Frontiers in cell and developmental biology · 2023Article
- A novel splice donor mutation inFrontiers in oncology · 2023Article
- Case report: Rubella virus-induced cutaneous granulomas in a girl with atypical SCID caused byFrontiers in genetics · 2023Article
- Structure and Function of SNM1 Family Nucleases.Advances in experimental medicine and biology · 2023Review
- Dynamics of the Artemis and DNA-PKcs Complex in the Repair of Double-Strand Breaks.Journal of molecular biology · 2022Review
- Structural analysis of the basal state of the Artemis:DNA-PKcs complex.Nucleic acids research · 2022Article
- Article
- Compound heterozygous DCLRE1C mutations lead to clinically typical Severe Combined Immunodeficiency presenting with Graft Versus Host Disease.Immunogenetics · 2021Article
- Structural and mechanistic insights into the Artemis endonuclease and strategies for its inhibition.Nucleic acids research · 2021Article
- Beyond monogenetic rare variants: tackling the low rate of genetic diagnoses in predominantly antibody deficiency.Cellular & molecular immunology · 2021Review
Corrections and comments
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Authors and funding
13 authors at 8 institutions in 6 countries.
Funding
Abstract
backgroundThe endonuclease ARTEMIS, which is encoded by the DCLRE1C gene, is a component of the nonhomologous end-joining pathway and participates in hairpin opening during the V(D)J recombination process and repair of a subset of DNA double-strand breaks. Patients with ARTEMIS deficiency usually present with severe combined immunodeficiency (SCID) and cellular radiosensitivity, but hypomorphic mutations can cause milder phenotypes (leaky SCID).
objectiveWe sought to correlate the functional effect of human DCLRE1C mutations on phenotypic presentation in patients with ARTEMIS deficiency.
methodsWe studied the recombination and DNA repair activity of 41 human DCLRE1C mutations in Dclre1c(-/-) v-abl kinase-transformed pro-B cells retrovirally engineered with a construct that allows quantification of recombination activity by means of flow cytometry. For assessment of DNA repair efficacy, resolution of γH2AX accumulation was studied after ionizing radiation.
resultsLow or absent activity was detected for mutations causing a typical SCID phenotype. Most of the patients with leaky SCID were compound heterozygous for 1 loss-of-function and 1 hypomorphic allele, with significant residual levels of recombination and DNA repair activity. Deletions disrupting the C-terminus result in truncated but partially functional proteins and are often associated with leaky SCID. Overexpression of hypomorphic mutants might improve the functional defect.
conclusionsCorrelation between the nature and location of DCLRE1C mutations, functional activity, and the clinical phenotype has been observed. Hypomorphic variants that have been reported in the general population can be disease causing if combined in trans with a loss-of-function allele. Therapeutic strategies aimed at inducing overexpression of hypomorphic alleles might be beneficial.
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