Somatic mosaicism in the Wiskott-Aldrich syndrome: molecular and functional characterization of genotypic revertants

Détails

ID Serval
serval:BIB_CCDB35D30104
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Somatic mosaicism in the Wiskott-Aldrich syndrome: molecular and functional characterization of genotypic revertants
Périodique
Clin Immunol
Auteur(s)
Davis B. R., Yan Q., Bui J. H., Felix K., Moratto D., Muul L. M., Prokopishyn N. L., Blaese R. M., Candotti F.
ISSN
1521-7035 (Electronic)
ISSN-L
1521-6616
Statut éditorial
Publié
Date de publication
04/2010
Volume
135
Numéro
1
Pages
72-83
Langue
anglais
Notes
Davis, Brian R
Yan, Qing
Bui, Jacquelin H
Felix, Kumar
Moratto, Daniele
Muul, Linda M
Prokopishyn, Nicole L
Blaese, R Michael
Candotti, Fabio
eng
R21 AI082327/AI/NIAID NIH HHS/
1R21AI082327/AI/NIAID NIH HHS/
Intramural NIH HHS/
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Clin Immunol. 2010 Apr;135(1):72-83. doi: 10.1016/j.clim.2009.12.011. Epub 2010 Feb 2.
Résumé
The reasons underlying the occurrence of multiple revertant genotypes in Wiskott-Aldrich syndrome (WAS) patients remain unclear. We have identified more than 30 revertant genotypes in a C995T WAS patient having 10-15% revertant, WAS protein (WASp)-expressing circulating lymphocytes. Of 497 allospecific T-cell clones generated from the peripheral blood, 47.1% carried a revertant sequence. All revertant T-cell clones exhibited restoration of WASp expression. However, anti-CD3-induced proliferative responses varied greatly amongst revertants. Several revertant T-cell clones expressed an internally deleted WASp mutant lacking much of the proline-rich region. This potentially accounts for the reduced anti-CD3 proliferative responses of these T-cell clones. We found no evidence for an increased DNA mutation rate in this patient. We conclude that the diversity of revertant genotypes in our patient does not result from an extraordinary mutation rate and that the amino acid sequence space explored by WASp in revertant T-cells is significantly smaller than might have been predicted from the diversity of revertant genotypes.
Mots-clé
Amino Acid Sequence, Base Sequence, Blotting, Western, Clone Cells, Genetic Variation, Genotype, Humans, *Mosaicism, RNA, Messenger/chemistry/genetics, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes/*immunology, Wiskott-Aldrich Syndrome/*genetics/immunology, Wiskott-Aldrich Syndrome Protein/*genetics/immunology
Pubmed
Création de la notice
01/11/2017 11:29
Dernière modification de la notice
03/03/2018 21:29
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