title: Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis.
abstract: 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.
authors.affiliation: 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.
authors.forename: Despina
authors.initials: D
authors.lastname: Moshous
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannetier
authors.forename: Régina de
authors.initials: Rd
authors.lastname: Chasseval Rd
authors.forename: Françoise le
authors.initials: Fl
authors.lastname: Deist Fl
authors.forename: Marina
authors.initials: M
authors.lastname: Cavazzana-Calvo
authors.forename: Serge
authors.initials: S
authors.lastname: Romana
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Macintyre
authors.forename: Danielle
authors.initials: D
authors.lastname: Canioni
authors.forename: Nicole
authors.initials: N
authors.lastname: Brousse
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Jean-Pierre de
authors.initials: JP
authors.lastname: Villartay
mesh_terms: 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*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C426344:DCLRE1C protein, human; D004720:Endonucleases; D001618:beta-Lactamases