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 clinical presentations 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.
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Funding
This work was supported by grants from National Natural Science Foundation of China (No. 81802491), Beijing Talent Fund (No. 2016000021469G201) and Beijing Municipal Science & Technology Commission (No. Z181100001718061).
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WM, JG, and JH designed most of the studies. WM carried out much of the work together with LG, JH, BX, and JG. WM, JG, and JH analyzed the data. WM wrote up the manuscript with input from JG and JH. All the authors read and approved the final manuscript.
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All patients (and/or their guardians) signed an informed consent to participate in this study, approved by the Ethics Committee of the Beijing Children’s Hospital, and to authorize the publication of clinical images.
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Mou, W., Gao, L., He, J. et al. Compound heterozygous DCLRE1C mutations lead to clinically typical Severe Combined Immunodeficiency presenting with Graft Versus Host Disease. Immunogenetics 73, 425–434 (2021). https://doi.org/10.1007/s00251-021-01219-4
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DOI: https://doi.org/10.1007/s00251-021-01219-4