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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
A novel form of human STAT1 deficiency impairing early but not late responses to interferons
Blood, Volume 116, No. 26, Year 2010
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Description
Autosomal recessive STAT1 deficiency is associated with impaired cellular responses to interferons and susceptibility to intracellular bacterial and viral infections. We report here a new form of partial STAT1 deficiency in 2 siblings presenting mycobacterial and viral diseases. Both carried a homozygous missense mutation replacing a lysine with an asparagine residue at position 201 (K201N) of STAT1. This mutation causes the abnormal splicing out of exon 8 from most STAT1 mRNAs, thereby decreasing (by ∼ 70%) STAT1 protein levels. The mutant STAT1 proteins are not intrinsically deleterious, in terms of tyrosine phosphorylation, dephosphorylation, homodimerization into γ-activating factor and heterotrimerization into ISGF-3, binding to specific DNA elements, and activation of the transcription. Interestingly, the activation of γ-activating factor and ISGF3 was impaired only at early time points in the various cells from patient (within 1 hour of stimulation), whereas sustained impairment occurs in other known forms of complete and partial recessive STAT1 deficiency. Consequently, delayed responses were normal; however, the early induction of interferon-stimulated genes was selectively and severely impaired. Thus, the early cellular responses to human interferons are critically dependent on the amount of STAT1 and are essential for the appropriate control of mycobacterial and viral infections. © 2010 by The American Society of Hematology.
Authors & Co-Authors
Kong, Xiao Fei
United States, New York
Rockefeller University
France, Paris
L'institut Des Maladies Génétiques Imagine
France, Paris
Université Paris Cité
China, Shanghai
Shanghai Jiao Tong University
Ciancanelli, Michael J.
United States, New York
Rockefeller University
Al-Hajjar, Sami Hussain
Saudi Arabia, Riyadh
College of Medicine
Saudi Arabia, Riyadh
King Faisal Specialist Hospital and Research Centre
Alsina, Laia
United States, Dallas
Baylor Institute for Immunology Research
Zumwalt, Timothy J.
United States, Dallas
Baylor Institute for Immunology Research
Bustamante, Jacinta Cecilia
France, Paris
L'institut Des Maladies Génétiques Imagine
France, Paris
Université Paris Cité
Feinberg, Jacqueline
France, Paris
L'institut Des Maladies Génétiques Imagine
France, Paris
Université Paris Cité
Audry, Magali
United States, New York
Rockefeller University
Prando, Carolina Cardoso De Mello
United States, New York
Rockefeller University
Bryant, Vanessa L.
United States, New York
Rockefeller University
Kreins, Alexandra Y.
United States, New York
Rockefeller University
United States, New York
Weill Cornell Graduate School of Medical Sciences
Bogunovic, Dusan
United States, New York
Rockefeller University
Halwani, Rabih
Saudi Arabia, Riyadh
College of Medicine
Zhang, Xinxin
China, Shanghai
Shanghai Jiao Tong University
Abel, Laurent
United States, New York
Rockefeller University
France, Paris
L'institut Des Maladies Génétiques Imagine
France, Paris
Université Paris Cité
Chaussabel, Damien
United States, Dallas
Baylor Institute for Immunology Research
Al-Muhsen, Saleh Zaid
Saudi Arabia, Riyadh
College of Medicine
Saudi Arabia, Riyadh
King Faisal Specialist Hospital and Research Centre
Casanova, Jean Laurent
United States, New York
Rockefeller University
France, Paris
L'institut Des Maladies Génétiques Imagine
France, Paris
Université Paris Cité
China, Shanghai
Shanghai Jiao Tong University
Saudi Arabia, Riyadh
College of Medicine
France, Paris
Hôpital Necker Enfants Malades
Boisson-Dupuis, Stéphanie
United States, New York
Rockefeller University
France, Paris
L'institut Des Maladies Génétiques Imagine
France, Paris
Université Paris Cité
Statistics
Citations: 19
Authors: 19
Affiliations: 9
Identifiers
Doi:
10.1182/blood-2010-04-280586.
ISSN:
00064971
Research Areas
Cancer
Genetics And Genomics
Health System And Policy