Reference : Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and...
Scientific journals : Article
Human health sciences : General & internal medicine
Life sciences : Genetics & genetic processes
http://hdl.handle.net/2268/134711
Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity.
English
Lopez-Herrera, Gabriela [> >]
Tampella, Giacomo [> >]
Pan-Hammarstrom, Qiang [> >]
Herholz, Peer [> >]
Trujillo-Vargas, Claudia M. [> >]
Phadwal, Kanchan [> >]
Simon, Anna Katharina [> >]
Moutschen, Michel mailto [Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén. >]
Etzioni, Amos [> >]
Mory, Adi [> >]
Srugo, Izhak [> >]
Melamed, Doron [> >]
Hultenby, Kjell [> >]
Liu, Chonghai [> >]
Baronio, Manuela [> >]
Vitali, Massimiliano [> >]
Philippet, Pierre [> >]
DIDEBERG, Vinciane mailto [Centre Hospitalier Universitaire de Liège - CHU > > Génétique >]
Aghamohammadi, Asghar [> >]
Rezaei, Nima [> >]
Enright, Victoria [> >]
Du, Likun [> >]
Salzer, Ulrich [> >]
Eibel, Hermann [> >]
Pfeifer, Dietmar [> >]
Veelken, Hendrik [> >]
Stauss, Hans [> >]
Lougaris, Vassilios [> >]
Plebani, Alessandro [> >]
Gertz, E. Michael [> >]
Schaffer, Alejandro A. [> >]
Hammarstrom, Lennart [> >]
Grimbacher, Bodo [> >]
2012
American Journal of Human Genetics
University of Chicago Press
90
6
986-1001
Yes (verified by ORBi)
International
0002-9297
1537-6605
Chicago
IL
[en] Adaptor Proteins, Signal Transducing/genetics ; Agammaglobulinemia/genetics ; Apoptosis ; Autoimmunity/genetics ; Autophagy ; B-Lymphocytes/cytology ; Cell Proliferation ; Child ; Child, Preschool ; Chromosome Mapping ; Female ; Genetic Linkage ; Genotype ; Homozygote ; Humans ; Immunologic Deficiency Syndromes/genetics ; Immunophenotyping ; Male ; Microscopy, Electron, Transmission/methods ; Models, Genetic ; Mutation ; Pedigree ; Phenotype
[en] Most autosomal genetic causes of childhood-onset hypogammaglobulinemia are currently not well understood. Most affected individuals are simplex cases, but both autosomal-dominant and autosomal-recessive inheritance have been described. We performed genetic linkage analysis in consanguineous families affected by hypogammaglobulinemia. Four consanguineous families with childhood-onset humoral immune deficiency and features of autoimmunity shared genotype evidence for a linkage interval on chromosome 4q. Sequencing of positional candidate genes revealed that in each family, affected individuals had a distinct homozygous mutation in LRBA (lipopolysaccharide responsive beige-like anchor protein). All LRBA mutations segregated with the disease because homozygous individuals showed hypogammaglobulinemia and autoimmunity, whereas heterozygous individuals were healthy. These mutations were absent in healthy controls. Individuals with homozygous LRBA mutations had no LRBA, had disturbed B cell development, defective in vitro B cell activation, plasmablast formation, and immunoglobulin secretion, and had low proliferative responses. We conclude that mutations in LRBA cause an immune deficiency characterized by defects in B cell activation and autophagy and by susceptibility to apoptosis, all of which are associated with a clinical phenotype of hypogammaglobulinemia and autoimmunity.
Researchers ; Professionals
http://hdl.handle.net/2268/134711
also: http://hdl.handle.net/2268/148014
10.1016/j.ajhg.2012.04.015
Copyright (c) 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

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