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The many faces of Artemis-deficient combined immunodeficiency — two patients with DCLRE1C mutations and a systematic literature review of genotype–phenotype correlation
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posted on 2023-06-08, 16:51 authored by Pamela P Lee, Lisa Woodbine, Kimberly C Gilmour, Shahnaz Bibi, Catherine M Cale, Persios J Amrolia, Paul A Veys, E Graham Davies, Penny Jeggo, Alison JonesDefective V(D)J recombination and DNA double-strand break (DSB) repair severely impair the development of T-lymphocytes and B-lymphocytes. Most patients manifest a severe combined immunodeficiency during infancy. We report 2 siblings with combined immunodeficiency (CID) and immunodysregulation caused by compound heterozygous Artemis mutations, including an exon 1–3 deletion generating a null allele, and a missense change (p.T71P). Skin fibroblasts demonstrated normal DSB repair by gamma-H2AX analysis, supporting the predicted hypomorphic nature of the p.T71P allele. In addition to these two patients, 12 patients with Artemis-deficient CID were previously reported. All had significant morbidities including recurrent infections, autoimmunity, EBV-associated lymphoma, and carcinoma despite having hypomorphic mutants with residual Artemis expression, V(D)J recombination or DSB repair capacity. Nine patients underwent stem cell transplant and six survived, while four patients who did not receive transplant died. The progressive nature of immunodeficiency and genomic instability accounts for poor survival, and early HSCT should be considered.
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Publication status
- Published
File Version
- Published version
Journal
Clinical ImmunologyISSN
1521-6616Publisher
ElsevierExternal DOI
Issue
3BVolume
149Page range
464-474Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
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- No
Peer reviewed?
- Yes
Legacy Posted Date
2014-03-12First Compliant Deposit (FCD) Date
2014-03-12Usage metrics
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