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16.11.2022 | Original Article

Clinical and Genetic Characterization of Patients with Artemis Deficiency in Japan

verfasst von: 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

Erschienen in: Journal of Clinical Immunology

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Abstract

Purpose

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.

Methods

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

Results

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.

Conclusion

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.
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Metadaten
Titel
Clinical and Genetic Characterization of Patients with Artemis Deficiency in Japan
verfasst von
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
Publikationsdatum
16.11.2022
Verlag
Springer US
Erschienen in
Journal of Clinical Immunology
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-022-01405-3

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