Clinical and Genetic Characterization of Patients with Artemis Deficiency in Japan

Kento Inoue, Satoshi Miyamoto, Dan Tomomasa, Eriko Adachi, Shohei Azumi, Yasuo Horikoshi, Takashi Ishihara, Shinya Osone, Yuta Kawahara, Ko Kudo, Zenichiro Kato, Hidenori Ohnishi, Kenichi Kashimada, Kohsuke Imai, Osamu Ohara, Menno C. van Zelm, Morton J. Cowan, Tomohiro Morio, Hirokazu Kanegane*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)



Artemis is an exonuclease essential for V(D)J recombination and repair of DNA double-stranded breaks. Pathogenic variants in DCLRE1C encoding Artemis cause TBNK+ severe combined immunodeficiency (SCID), and patients with Artemis-deficient SCID (ART-SCID) require definitive therapy with allogeneic hematopoietic cell transplantation (HCT). Here we describe the clinical and genetic characteristics of patients with ART-SCID who were diagnosed in Japan from 2003 to 2022. 


Clinical data of ART-SCID patients who were diagnosed between 2003 and 2022 in Japan were collected from their physicians using a questionnaire. 


ART-SCID diagnosis was made in eight patients from seven families with severe infections within 6 months of life. Two patients had missense variants, five patients had large genomic deletions, and one patient was compound heterozygous for a missense variant and large genomic deletion. All eight underwent allogeneic HCT within 4 months after the diagnosis, 7 receiving a conditioning regimen containing alkylating agents, and one patient without conditioning due to uncontrolled infection. Two patients with poor performance status (PS) died of complications 410 days and 32 days post-HCT, respectively. Of the six surviving patients with a median follow-up time of 8.3 (0.5–17.9) years, three patients had growth retardation. The patients with PS of 0–2 showed a tendency for better overall survival than those with PS 3–4. 


Large deletions were the most common genetic cause of ART-SCID in Japan. To improve HCT outcome, early diagnosis with newborn screening for SCID is urgently needed.

Original languageEnglish
Pages (from-to)585-594
Number of pages10
JournalJournal of Clinical Immunology
Issue number3
Publication statusPublished - 16 Nov 2023
Externally publishedYes

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Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.


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