title: Novel Artemis gene mutations of radiosensitive severe combined immunodeficiency in Japanese families.
abstract: A subgroup of patients with severe combined immunodeficiency (SCID) and increased cellular radiation sensitivity (RS-SCID) have mutations of Artemis, a gene that encodes a protein essential for V(D)J recombination and DNA double-strand break repair. RS-SCID described to date are either of European origin or are Athabascan-speaking native Americans belonging to the Navajo and Apache tribes. We have identified three Japanese boys and one girl from four unrelated families with RS-SCID caused by a genomic exon 3 deletion of the Artemis gene, resulting in loss of exon 3 and skipping of exon 4. Two patients were homozygous and two patients were heterozygous for this novel mutation. Those parents studied were heterozygous for this mutation. These findings suggest the genomic exon 3 deletion is unique to Japan and may be considered as a founder haplotype. Although two infants underwent successful bone marrow transplantation and immune reconstitution, the long-term outcome of this procedure is uncertain, because Artemis is expressed in most tissues and lack of its function in cells other than those derived from hematopoietic stem cells may increase the risk of malignancies.
authors.affiliation: Department of Pediatrics, Shinshu University School of Medicine, Asahi 3-1-1, 390-8621 Matsumoto, Japan.
authors.forename: Norimoto
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Kazunaga
authors.initials: K
authors.lastname: Agematsu
authors.forename: Kanji
authors.initials: K
authors.lastname: Sugita
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sako
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nonoyama
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yachie
authors.forename: Satoru
authors.initials: S
authors.lastname: Kumaki
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: Hans D
authors.initials: HD
authors.lastname: Ochs
authors.forename: Katsuo
authors.initials: K
authors.lastname: Sugita
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Fukushima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Komiyama
mesh_terms: D015703:Antigens, CD / Q000097:blood; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D004268:DNA-Binding Proteins; D004720:Endonucleases; D005091:Exons / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000528:radiation effects; D018703:Founder Effect; D016368:Frameshift Mutation; D017353:Gene Deletion; D006239:Haplotypes; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007223:Infant; D007564:Japan; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D009687:Nuclear Proteins; C426344:DCLRE1C protein, human; D004720:Endonucleases