V(D)J recombination defects in lymphocytes due to RAG mutations: severe immunodeficiency with a spectrum of clinical presentations

Citation
A. Villa et al., V(D)J recombination defects in lymphocytes due to RAG mutations: severe immunodeficiency with a spectrum of clinical presentations, BLOOD, 97(1), 2001, pp. 81-88
Citations number
28
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Hematology,"Cardiovascular & Hematology Research
Journal title
BLOOD
ISSN journal
0006-4971 → ACNP
Volume
97
Issue
1
Year of publication
2001
Pages
81 - 88
Database
ISI
SICI code
0006-4971(20010101)97:1<81:VRDILD>2.0.ZU;2-6
Abstract
Severe combined immunodeficiency (SCID) comprises a heterogeneous group of primary immunodeficiencies, a proportion of which are due to mutations in e ither of the 2 recombination activating genes (RAG)-1 and -2, which mediate the process of V(D)J recombination leading to the assembly of antigen rece ptor genes. It is reported here that the clinical and immunologic phenotype s of patients bearing mutations in RAGs are more diverse than previously th ought and that this variability is related, in part, to the specific type o f RAG mutation. By analyzing 44 such patients from 41 families, the followi ng conclusions were reached: (1) null mutations on both alleles lead to the T-B-SCID phenotype; (2) patients manifesting classic Omenn syndrome (OS) h ave missense mutations on at least one allele and maintain partial V(D)J re combination activity, which accounts for the generation of residual, oligoc lonal lymphocytes; (3) in a third group of patients, findings were only par tially compatible with OS, and these patients, who also carried at least on e missense mutation, may be considered to have atypical SCID/OS; (4) patien ts with engraftment of maternal T cells as a complication of a transplacent al transfusion represented a fourth group, and these patients, who often pr esented with a clinical phenotype mimicking OS, may be observed regardless of the type of RAG gene mutation. Analysis of the HAG genes by direct seque ncing is an effective way to provide accurate diagnosis of RAG-deficient as opposed to RAG-independent V(D)J recombination defects, a distinction that cannot be made based on clinical and immunologic phenotype alone. (C) 2001 by The American Society of Hematology.