Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis

We have previously described the identification of Artemis, a factor involved in the nonhomologous end joining (NHEJ) phase of V(D)J recombination of T and B cell receptor genes. Null mutations of the Artemis gene result in a complete absence of T and B lymphocytes that is associated with increased...

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Bibliographic Details
Published in:The Journal of clinical investigation 2003-02, Vol.111 (3), p.381-387
Main Authors: Moshous, Despina, Pannetier, Christophe, Chasseval Rd, Régina de, Deist Fl, Françoise le, Cavazzana-Calvo, Marina, Romana, Serge, Macintyre, Elizabeth, Canioni, Danielle, Brousse, Nicole, Fischer, Alain, Casanova, Jean-Laurent, Villartay, Jean-Pierre de
Format: Article
Language:English
Subjects:
Adolescent
B-Lymphocytes - immunology
beta-Lactamases - genetics
Biomedical research
Blotting, Southern
Child
Child, Preschool
Endonucleases
Family Health
Female
Fibroblasts - metabolism
Flow Cytometry
Genetic Predisposition to Disease
Humans
Immunohistochemistry
Immunologic Deficiency Syndromes - genetics
Immunologic Deficiency Syndromes - immunology
Infant
Lymphoma - etiology
Lymphoma, B-Cell - genetics
Male
Mutation
Nuclear Proteins
Polymerase Chain Reaction
Severe Combined Immunodeficiency - genetics
T-Lymphocytes - immunology
Time Factors
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Summary:We have previously described the identification of Artemis, a factor involved in the nonhomologous end joining (NHEJ) phase of V(D)J recombination of T and B cell receptor genes. Null mutations of the Artemis gene result in a complete absence of T and B lymphocytes that is associated with increased cell radiosensitivity, causing the radiosensitive T(-)B(-) SCID (RS-SCID) condition. We presently report the occurrence of hypomorphic mutations of the Artemis gene in four patients from two kindreds. Partially preserved in vivo activity of Artemis is associated with the presence of polyclonal T and B lymphocyte populations, albeit in reduced numbers, along with chromosomal instability and development of EBV-associated lymphoma in two of four patients. This syndrome emphasizes the role of Artemis in the NHEJ pathway of DNA repair and suggests that other, yet ill-defined, conditions associating immunodeficiency and lymphoma could be caused by mutations in genes encoding NHEJ factors.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI16774