Compound heterozygous DCLRE1Cmutations lead to clinically typical Severe CombinedImmunodeficiency presenting with Graft Versus Host Disease.

Abstract

Artemis (DCLRE1C) is involved in opening recombination-activating gene (RAG1/RAG2)-generated hairpins during V(D)J recombination, an essential process for the differentiation and maturation of T and B cells. Here, we reported a case of 5-month-old boy with recurrent respiratory infections, disseminated Bacille Calmette-Guérin (BCG) infection, generalized erythroderma, hepatosplenomegaly, lymphadenopathy, eosinophillia and failure to thrive, symptoms often observed in Omenn syndrome. Genetic analysis revealed compound heterozygous mutations of the DCLRE1C gene, including deletions of exons 1 and 2, and a c.352G>T (p.G118X) nonsense mutation in exon 5. Flow cytometry analysis of the patient PBMCs indicated a TlowB-NK+ immunophenotype. Short tandem repeat (STR) analysis confirmed transplacental maternal lymphocytes engraftment in circulating blood of the patient. Collectively, we reported a patient showing atypical immunophenotypic and typical clinicalpresentations of Severe Combined Immunodeficiency (SCID) with Graft Versus Host Disease (GVHD) in the context of compound heterozygous mutations of the DCLRE1C gene. This study adds to the ever-growing knowledge on the broad immunological and clinical spectrum associated with DCLRE1C mutations.