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 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.
Moshous
Despina
D
Unité Développement Normal et Pathologique du Système Immunitaire, Institut National de la Santé et de la Recherche Médicale (INSERM) U429, Hôpital Necker Enfants-Malades, Paris, France.
Pannetier
Christophe
C
Chasseval Rd
Régina de
Rd
Deist Fl
Françoise le
Fl
Cavazzana-Calvo
Marina
M
Romana
Serge
S
Macintyre
Elizabeth
E
Canioni
Danielle
D
Brousse
Nicole
N
Fischer
Alain
A
Casanova
Jean-Laurent
JL
Villartay
Jean-Pierre de
JP
D000293:Adolescent; D001402:B-Lymphocytes / Q000276:immunology*; D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins; D004720:Endonucleases; D005192:Family Health; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology*; D007223:Infant; D008223:Lymphoma / Q000209:etiology*; D016393:Lymphoma, B-Cell / Q000235:genetics; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D016511:Severe Combined Immunodeficiency / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D001618:beta-Lactamases / Q000235:genetics*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C426344:DCLRE1C protein, human; D004720:Endonucleases; D001618:beta-Lactamases