Advanced

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

Villa, A; Sobacchi, C; Notarangelo, LD; Bozzi, F; Abinun, M; Abrahamsen, TG; Arkwright, PD; Baniyash, M; Brooks, EG and Conley, ME, et al. (2001) In Blood 97(1). p.81-88
Abstract
Severe combined immunodeficiency (SCID) comprises a heterogeneous group of primary immunodeficiencies, a proportion of which are due to mutations in either 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 receptor genes. It is reported here that the clinical and immunologic phenotypes of patients bearing mutations in RAGs are more diverse than previously thought and that this variability is related, in part, to the specific type of RAG mutation. By analyzing 44 such patients from 41 families, the following conclusions were reached: (1) null mutations on both alleles lead to the T-B-SCID phenotype; (2) patients manifesting classic Omenn syndrome (OS)... (More)
Severe combined immunodeficiency (SCID) comprises a heterogeneous group of primary immunodeficiencies, a proportion of which are due to mutations in either 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 receptor genes. It is reported here that the clinical and immunologic phenotypes of patients bearing mutations in RAGs are more diverse than previously thought and that this variability is related, in part, to the specific type of RAG mutation. By analyzing 44 such patients from 41 families, the following conclusions were reached: (1) null mutations on both alleles lead to the T-B-SCID phenotype; (2) patients manifesting classic Omenn syndrome (OS) have missense mutations on at least one allele and maintain partial V(D)J recombination activity, which accounts for the generation of residual, oligoclonal lymphocytes; (3) in a third group of patients, findings were only partially compatible with OS, and these patients, who also carried at least one missense mutation, may be considered to have atypical SCID/OS; (4) patients with engraftment of maternal T cells as a complication of a transplacental transfusion represented a fourth group, and these patients, who often presented with a clinical phenotype mimicking OS, may be observed regardless of the type of RAG gene mutation. Analysis of the HAG genes by direct sequencing 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. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
97
issue
1
pages
81 - 88
publisher
American Society of Hematology
external identifiers
  • wos:000166177300009
  • scopus:0035161258
ISSN
1528-0020
DOI
10.1182/blood.V97.1.81
language
English
LU publication?
no
id
bbb28579-f1a3-4505-b866-96b8622cceae (old id 3851768)
date added to LUP
2013-06-28 15:26:40
date last changed
2018-03-18 03:53:53
@article{bbb28579-f1a3-4505-b866-96b8622cceae,
  abstract     = {Severe combined immunodeficiency (SCID) comprises a heterogeneous group of primary immunodeficiencies, a proportion of which are due to mutations in either 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 receptor genes. It is reported here that the clinical and immunologic phenotypes of patients bearing mutations in RAGs are more diverse than previously thought and that this variability is related, in part, to the specific type of RAG mutation. By analyzing 44 such patients from 41 families, the following conclusions were reached: (1) null mutations on both alleles lead to the T-B-SCID phenotype; (2) patients manifesting classic Omenn syndrome (OS) have missense mutations on at least one allele and maintain partial V(D)J recombination activity, which accounts for the generation of residual, oligoclonal lymphocytes; (3) in a third group of patients, findings were only partially compatible with OS, and these patients, who also carried at least one missense mutation, may be considered to have atypical SCID/OS; (4) patients with engraftment of maternal T cells as a complication of a transplacental transfusion represented a fourth group, and these patients, who often presented with a clinical phenotype mimicking OS, may be observed regardless of the type of RAG gene mutation. Analysis of the HAG genes by direct sequencing 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.},
  author       = {Villa, A and Sobacchi, C and Notarangelo, LD and Bozzi, F and Abinun, M and Abrahamsen, TG and Arkwright, PD and Baniyash, M and Brooks, EG and Conley, ME and Cortes, P and Duse, M and Fasth, A and Filipovich, AM and Infante, AJ and Jones, A and Mazzolari, E and Muller, SM and Pasic, S and Rechavi, G and Sacco, MG and Santagata, S and Schroeder, ML and Seger, R and Strina, D and Ugazio, A and Valiaho, J and Vihinen, Mauno and Vogler, LB and Ochs, H and Vezzoni, P and Friedrich, W and Schwarz, K},
  issn         = {1528-0020},
  language     = {eng},
  number       = {1},
  pages        = {81--88},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {V(D)J recombination defects in lymphocytes due to RAG mutations: severe immunodeficiency with a spectrum of clinical presentations},
  url          = {http://dx.doi.org/10.1182/blood.V97.1.81},
  volume       = {97},
  year         = {2001},
}