The many faces of Artemis-deficient combined immunodeficiency — two patients with DCLRE1C mutations and a systematic literature review of genotype–phenotype correlation

Lee, Pamela P, Woodbine, Lisa, Gilmour, Kimberly C, Bibi, Shahnaz, Cale, Catherine M, Amrolia, Persios J, Veys, Paul A, Davies, E Graham, Jeggo, Penny A and Jones, Alison (2013) The many faces of Artemis-deficient combined immunodeficiency — two patients with DCLRE1C mutations and a systematic literature review of genotype–phenotype correlation. Clinical Immunology, 149 (3B). pp. 464-474. ISSN 1521-6616

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Abstract

Defective 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.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science
Depositing User: Gee Wheatley
Date Deposited: 12 Mar 2014 07:15
Last Modified: 07 Mar 2017 07:12
URI: http://sro.sussex.ac.uk/id/eprint/47813

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