Positive newborn screen: a case of a novel variant in DCLRE1C in a patient with SCID
Abstract
Background: Artemis enzyme, encoded by the DCLRE1C gene, is essential to V(D)J recombination in both T and B lymphocytes. Artemis functions as an important component of the nonhomologous end-joining DNA double-strand break repair pathway. Artemis deficiency leads to a T-B-NK+ severe combined immune deficiency (SCID) associated with radiosensitivity.
Clinical presentation: We present a case of a positive newborn screen for SCID in a patient who was subsequently shown to have a T-B-NK+ phenotype. Further immune evaluation showed profound T and B lymphopenia, near-absent response to mitogen stimulation, and absent immunoglobulins A and M. Genetic investigation demonstrated a novel and putative pathogenic variant in the DCLRE1C gene.
Conclusion: This case identifies a novel variant in the DCLRE1C gene in a patient with SCID identified by newborn screening.
Statement of novelty: This case report identifies a novel variant in the DCLRE1C gene in a patient with T-B-NK+ SCID.
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REFERENCES
Felgentreff K., Lee Y.N., Frugoni F., Du L., van der Burg M., Giliani S., Tezcan I., Reisli I., Mejstrikova E., de Villartay J.P., Sleckman B.P., Manis J., and Notarangelo L.D. 2015. Functional analysis of naturally occurring DCLRE1C mutations and correlation with the clinical phenotype of ARTEMIS deficiency. J. Allergy Clin. Immunol. 136(1):140–150.e7.
Lee P.P., Woodbine L., Gilmour K.C., Bibi S., Cale C.M., Amrolia P.J., Veys P.A., Davies E.G., Jeggo P.A., and Jones A. 2013. The many faces of Artemis-deficient combined immunodeficiency—Two patients with DCLRE1C mutations and a systematic literature review of genotype–phenotype correlation. Clin. Immunol. 149(3):464–474.
Mancebo E., Recio M.J., Martínez-Busto E., González-Granado L.I., Rojo P., Fernández-Díaz E., Ruiz-Contreras J., Paz-Artal E., and Allende L.M. 2011. Possible role of Artemis c.512C>G polymorphic variant in Omenn syndrome. DNA Repair. 10(1):3–4.
Moshous D., Callebaut I., Chasseval R., Corneo B., Cavazzana-Calvo M., Le Deist F., Tezcan I., Sanal O., Bertrand Y., Philippe N., Fischer A., and de Villartay J.-P. 2001. Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency. Cell. 105(4):177–186.
Pannicke U., Hönig M., Schulze I., Rohr J., Heinz G.A., Braun S., Janz I., Rump E.M., Seidel M.G., Matthes-Martin S., Soerensen J., Greil J., Stachel D.K., Belohradsky B.H., Albert M.H., Schulz A., Ehl S., Friedrich W., and Schwarz K. 2010. The most frequent DCLRE1C (ARTEMIS) mutations are based on homologous recombination events. Hum. Mutat. 31(2):197–207.
Sundin M., Marits P., Ramme K., Kolios A.G., and Nilsson J. 2019. Severe combined immunodeficiency (SCID) presenting in childhood, with agammaglobulinemia, associated with novel compound heterozygous mutations in DCLRE1C. Clin. Immunol. 200:16–18.
Woodbine L., Grigoriadou S., Goodarzi A.A., Riballo E., Tape C., Oliver A.W., van Zelm M.C., Buckland M.S., Davies E.G., Pearl L.H., and Jeggo P.A. 2010. An Artemis polymorphic variant reduces Artemis activity and confers cellular radiosensitivity. DNA Repair. 9(9):1003–1010.
Information & Authors
Information
Published In
LymphoSign Journal
Volume 7 • Number 1 • March 2020
Pages: 46 - 48
History
Received: 8 January 2020
Accepted: 28 January 2020
Accepted manuscript online: 10 March 2020
Copyright
© 2020.
Authors
Competing Interests
Dr. Brager has received honoraria from Takeda and Sanofi.
Funding Information
This case report was not funded.
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NoreenChoe, LaurenBrick, MariyaKozenko, PraneshChakraborty, Kristin D.Kernohan, DennisBulman, and RaeBrager. 2020. Positive newborn screen: a case of a novel variant in DCLRE1C in a patient with SCID. LymphoSign Journal.
7(1): 46-48. https://doi.org/10.14785/lymphosign-2020-0001
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