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ID 119390
Title Alternative
Three novel forms of autosomal recessive TYK2 deficiency
Author
Ogishi, Masato The Rockefeller University
Arias, Andrés Augusto The Rockefeller University|University of Antioquia
Yang, Rui The Rockefeller University
Han, Ji Eun The Rockefeller University
Zhang, Peng The Rockefeller University
Rinchai, Darawan The Rockefeller University
Halpern, Joshua The Rockefeller University
Mulwa, Jeanette The Rockefeller University
Keating, Narelle The Rockefeller University|University of Melbourne
Chrabieh, Maya INSERM U1163|Paris Cité University
Lainé, Candice INSERM U1163|Paris Cité University
Seeleuthner, Yoann INSERM U1163|Paris Cité University
Ramírez-Alejo, Noé The Rockefeller University
Nekooie-Marnany, Nioosha Isfahan University of Medical Sciences
Guennoun, Andrea Sidra Medicine
Muller-Fleckenstein, Ingrid University of Erlangen-Nuremberg
Fleckenstein, Bernhard University of Erlangen-Nuremberg
Kilic, Sara S. Uludag University
Ehl, Stephan University of Freiburg
Kaiser-Labusch, Petra Klinikum Bremen–Mitte
Kendir-Demirkol, Yasemin Umraniye Training and Research Hospital, University of Health Sciences
Rozenberg, Flore Cochin Hospital
Errami, Abderrahmane Hassan II University
Zhang, Shen-Ying The Rockefeller University|INSERM U1163|Paris Cité University
Zhang, Qian The Rockefeller University|INSERM U1163|Paris Cité University
Bohlen, Jonathan INSERM U1163|Paris Cité University
Philippot, Quentin INSERM U1163|Paris Cité University
Puel, Anne The Rockefeller University|INSERM U1163|Paris Cité University
Jouanguy, Emmanuelle The Rockefeller University|INSERM U1163|Paris Cité University
Pourmoghaddas, Zahra Isfahan University of Medical Sciences
Bakhtiar, Shahrzad University Hospital Frankfurt
Willasch, Andre M. University Hospital Frankfurt
Horneff, Gerd Asklepios Clinic Sankt Augustin|University of Cologne
Llanora, Genevieve National University Health System
Shek, Lynette P. National University Health System|National University of Singapore
Chai, Louis Y.A. National University Health System|National University of Singapore
Tay, Sen Hee National University of Singapore|National University Hospital
Rahimi, Hamid H. Isfahan University of Medical Sciences
Mahdaviani, Seyed Alireza Shahid Beheshti University of Medical Sciences
Nepesov, Serdar Istanbul Medipol University
Bousfiha, Aziz A. King Hassan II University
Erdeniz, Emine Hafize Ondokuz Mayıs University
Karbuz, Adem University of Health Sciences
Marr, Nico Sidra Medicine
Navarrete, Carmen Hospital de Niños Roberto del Río
Adeli, Mehdi Sidra Medicine|Hamad Medical Corp.
Hammarstrom, Lennart Karolinska Institute|Beijing Genomics Institute|Tehran University of Medical Sciences
Abolhassani, Hassan Karolinska Institute|Tehran University of Medical Sciences
Parvaneh, Nima Tehran University of Medical Sciences
Muhsen, Saleh Al King Saud University
Alosaimi, Mohammed F. King Saud University
Alsohime, Fahad King Saud University|King Saud University Medical City
Nourizadeh, Maryam Tehran University of Medical Sciences
Moin, Mostafa Tehran University of Medical Sciences
Arnaout, Rand King Faisal Specialist Hospital and Research Center|Al Faisal University
Alshareef, Saad King Faisal Specialist Hospital and Research Center
El-Baghdadi, Jamila Mohamed V Military Hospital
Genel, Ferah University of Health Sciences, Dr Behçet Uz Children’s Hospital
Sherkat, Roya Isfahan University of Medical Sciences
Kiykim, Ayça Istanbul University-Cerrahpasa
Yücel, Esra Istanbul University
Keles, Sevgi Necmettin Erbakan University
Bustamante, Jacinta The Rockefeller University|INSERM U1163|Necker Hospital for Sick Children
Abel, Laurent The Rockefeller University|INSERM U1163|Paris Cité University
Casanova, Jean-Laurent The Rockefeller University|INSERM U1163|Paris Cité University|Howard Hughes Medical Institute|Necker Hospital for Sick Children
Boisson-Dupuis, Stéphanie The Rockefeller University|INSERM U1163|Paris Cité University
Content Type
Journal Article
Description
Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-α/β (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the commonP1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V). All these missense alleles encode detectable proteins. The R864C and G1010D alleles are hypomorphic and loss-of-function (LOF), respectively, across signaling pathways. By contrast, hypomorphic G996R, G634E, and A928V mutations selectively impair responses to IL-23, like P1104A. Impairment of the IL-23–dependent induction of IFN-γ is the only mechanism of mycobacterial disease common to patients with complete TYK2 deficiency with or without TYK2 expression, partial TYK2 deficiency across signaling pathways, or rare or common partial TYK2 deficiency specific for IL-23 signaling.
Journal Title
Journal of Experimental Medicine
ISSN
00221007
15409538
NCID
AA00697559
AA12119243
Publisher
Rockefeller University Press
Volume
219
Issue
10
Start Page
e20220094
Published Date
2022-09-12
Rights
This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Institute of Advanced Medical Sciences