A loss-of-function <i>IFNAR1</i> allele in Polynesia underlies severe viral diseases in homozygotes

Jean-Laurent Casanova; Andrew Wood; Lluis Quintana-Murci; Ryan Minster; Andrés Moreno-Estrada; Laurent Abel; Paul Gray; Emmanuelle Jouanguy; Shen-Ying Zhang; Stuart Tangye; Van-Mai Cao-Lormeau; Maite Aubry; Iotefa Teiti; Rohan Ameratunga; Richard King; Cheng-Yee Chan; Adrian Hill; Kylie Drake; See-Tarn Woon; Kate Gibson; Simon Stables; Sarah Primhak; Annaliesse Blincoe; Jane Peake; Vanessa Sarkozy; Peter Mcnaughton; Take Naseri; Muagututi‘a Reupena; Satupa‘itea Viali; Litara Esera Tulifau; Ranjan Deka; Vivien Béziat; Evelyne Jacqz Aigrain; Tiphaine Adam de Beaumais; Marianne Besnard; Sylvain Latour; Zineb Sbihi; Lazaro Lorenzo; Sandra Pellegrini; Gilles Uzé; Zhi Li; Benedetta Bigio; Yoann Seeleuthner; Boubacar Coulibaly; Kathryn Robson; Alexander Mentzer; Erika Hagelberg; Consuelo Quinto-Cortés; Carmina Barberena-Jonas; Karla Sandoval; Stephen Mcgarvey; Daniel Weeks; Nicola Hawley; Maguelonne Roux; Christine Harmant; Marie Materna; Lucy Bizien; Adrian Gervais; Jie Chen; Emma Best; Jeremy Choin; Qian Zhang; Kuang-Chih Hsiao; Paul Bastard

doi:10.1084/jem.20220028

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A loss-of-function <i>IFNAR1</i> allele in Polynesia underlies severe viral diseases in homozygotes

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A loss-of-function IFNAR1 allele in Polynesia underlies severe viral diseases in homozygotes

Jean-Laurent Casanova, Andrew Wood, Lluis Quintana-Murci, Ryan Minster, Andrés Moreno-Estrada, Laurent Abel, Paul Gray, Emmanuelle Jouanguy, Shen-Ying Zhang, Stuart Tangye, …

Journal of Experimental Medicine, Vol.219(6)

06/2022

DOI: https://doi.org/10.1084/jem.20220028

PMCID: PMC9026234

PMID: 35442418

Abstract

Human disease genetics

Immunodeficiency

Infectious disease and host defense

Innate immunity and inflammation

Human disease genetics

Globally, autosomal recessive IFNAR1 deficiency is a rare inborn error of immunity underlying susceptibility to live attenuated vaccine and wild-type viruses. We report seven children from five unrelated kindreds of western Polynesian ancestry who suffered from severe viral diseases. All the patients are homozygous for the same nonsense IFNAR1 variant (p.Glu386*). This allele encodes a truncated protein that is absent from the cell surface and is loss-of-function. The fibroblasts of the patients do not respond to type I IFNs (IFN-α2, IFN-ω, or IFN-β). Remarkably, this IFNAR1 variant has a minor allele frequency >1% in Samoa and is also observed in the Cook, Society, Marquesas, and Austral islands, as well as Fiji, whereas it is extremely rare or absent in the other populations tested, including those of the Pacific region. Inherited IFNAR1 deficiency should be considered in individuals of Polynesian ancestry with severe viral illnesses.

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Title: A loss-of-function IFNAR1 allele in Polynesia underlies severe viral diseases in homozygotes
Creators - without role: Jean-Laurent Casanova - Rockefeller University
Andrew Wood - Starship Children's Health
Lluis Quintana-Murci - Collège de France
Ryan Minster - University of Pittsburgh
Andrés Moreno-Estrada - Center for Research and Advanced Studies of the National Polytechnic Institute
Laurent Abel - Inserm
Paul Gray - UNSW Sydney
Emmanuelle Jouanguy - Inserm
Shen-Ying Zhang - Rockefeller University
Stuart Tangye - Garvan Institute of Medical Research
Van-Mai Cao-Lormeau - Institut Louis Malardé
Maite Aubry - Institut Louis Malardé
Iotefa Teiti - Institut Louis Malardé
Rohan Ameratunga - Auckland City Hospital
Richard King - Canterbury Health Laboratories
Cheng-Yee Chan - Canterbury Health Laboratories
Adrian Hill - University of Oxford
Kylie Drake - Canterbury Health Laboratories
See-Tarn Woon - Auckland City Hospital
Kate Gibson
Simon Stables - Auckland City Hospital
Sarah Primhak - Starship Children's Health
Annaliesse Blincoe - Starship Children's Health
Jane Peake - Queensland Children’s Hospital
Vanessa Sarkozy - Sydney Children's Hospital
Peter Mcnaughton - Queensland Children’s Hospital
Take Naseri - Brown University
Muagututi‘a Reupena - National University of Samoa
Satupa‘itea Viali
Litara Esera Tulifau - Tupua Tamasese Meaole Hospital
Ranjan Deka - University of Cincinnati Medical Center
Vivien Béziat - Institut des Maladies Génétiques Imagine
Evelyne Jacqz Aigrain - Hôpital Saint-Louis
Tiphaine Adam de Beaumais - Institut Gustave Roussy
Marianne Besnard - University of French Polynesia
Sylvain Latour - Inserm
Zineb Sbihi - Institut des Maladies Génétiques Imagine
Lazaro Lorenzo - Inserm
Sandra Pellegrini - Institut Pasteur
Gilles Uzé - Université de Montpellier, Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
Zhi Li - Inserm
Benedetta Bigio - Rockefeller University
Yoann Seeleuthner - Inserm
Boubacar Coulibaly - Inserm
Kathryn Robson - MRC Weatherall Institute of Molecular Medicine
Alexander Mentzer - Centre for Human Genetics
Erika Hagelberg - University of Oslo
Consuelo Quinto-Cortés - Center for Research and Advanced Studies of the National Polytechnic Institute
Carmina Barberena-Jonas - Center for Research and Advanced Studies of the National Polytechnic Institute
Karla Sandoval - Center for Research and Advanced Studies of the National Polytechnic Institute
Stephen Mcgarvey - Brown University
Daniel Weeks - University of Pittsburgh
Nicola Hawley - Yale University
Maguelonne Roux - Institut Pasteur
Christine Harmant - Université Paris Cité
Marie Materna - Institut des Maladies Génétiques Imagine
Lucy Bizien - Inserm
Adrian Gervais - Université Paris Cité
Jie Chen - Rockefeller University
Emma Best - Starship Children's Health
Jeremy Choin - Institut Pasteur
Qian Zhang - Rockefeller University
Kuang-Chih Hsiao - University of Auckland
Paul Bastard - Assistance Publique – Hôpitaux de Paris
Publication Details: Journal of Experimental Medicine, Vol.219(6)
Grant note: The laboratory of V.-M. Cao-Lormeau is supported by MATAEA grant no. 03557/MED/REC_29/05/2019 (Délégation à la recherche de la Polynésie française). The Laboratory of Human Evolutionary Genetics is supported by Institut Pasteur, Collège de France, the Centre national de la recherche scientifique, Fondation Allianz-Institut de France, the French Government’s Investissement d’Avenir program, Laboratoires d’Excellence “Integrative Biology of Emerging Infectious Diseases” (ANR-10-LABX-62-IBEID) and “Milieu Intérieur” (ANR-10-LABX-69-01), Fondation de France (grant no. 00106080), and Fondation pour la Recherche Médicale (Equipe FRM DEQ20180339214). The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH; R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, the NIH Clinical and Translational Science Award program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics, and the Genome Sequencing Program Coordinating Center funded by the National Human Genome Research Institute (UM1HG006504 and U24HG008956); the Yale High-Performance Computing Center (S10OD018521); the Fisher Center for Alzheimer’s Research Foundation; the Meyer Foundation; the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01); the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID); the French Foundation for Medical Research (FRM; EQU201903007798); the FRM and ANR GENCOVID project; the ANRS-COV05, ANR GENVIR (ANR-20-CE93-003), and ANR AABIFNCOV (ANR-20-CO11-0001) projects; the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the Square Foundation, Grandir - Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, INSERM, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), and the University of Paris. P. Bastard was supported by the FRM (EA20170638020) and by the MD-PhD program of the Imagine Institute (with the support of Fondation Bettencourt-Schueller). The National Laboratory of Genomics for Biodiversity (LANGEBIO-CINVESTAV) in Mexico is supported by Consejo Nacional de Ciencia y Technologia (grant number FONCICYT/50/2016), The Newton Fund through the Medical Research Council (grant number MR/N028937/1), and the International Center for Genetic Engineering and Biotechnology grant number CRP/MEX20-01, awarded to A. Moreno-Estrada. S.G. Tangye is supported by a Leadership 3 Investigator Grant awarded by the National Health and Medical Research Council of Australia (1176665) and the Jeffrey Modell Foundation. Clinical Immunogenomics Research Consortium Australasia investigators (K.-C. Hsiao, P. McNaughton, A. Blincoe, J. Peake, S.G. Tangye, and P. Gray) are supported by the John Brown Cook Foundation. This work was supported by the National Institutes of Health grants R01-HL093093 (S.T. McGarvey) and R01-HL133040 (R.L. Minster). Molecular data for the Trans-Omics in Precision Medicine (TOPMed) program were provided by the National Heart, Lung, and Blood Institute (NHLBI). Genome sequencing for the Soifua Manuia study, labeled “NHLBI TOPMed: Genome-wide Association Study of Adiposity in Samoans” (phs000972.v4.p1) in the dbGaP, was performed at the Northwest Genomics Center (HHSN268201100037C) and the New York Genome Center (HHSN268201500016C). Core support, including centralized genomic read mapping and genotype calling, along with variant quality metrics and filtering, was provided by the TOPMed Informatics Research Center (3R01-HL117626-02S1; contract HHSN268201800002I). Core support, including phenotype harmonization, data management, sample-identity QC, and general program coordination, was also provided by the TOPMed Data Coordinating Center (R01-HL120393; U01-HL120393; contract HHSN268201800001I). We gratefully acknowledge the studies and participants who provided biological samples and data for TOPMed. This research was funded in whole or in part by the French National Research Agency (ANR).
Identifiers: 9936712309311
Academic Unit: Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
Language: English
Resource Type: Journal article
Local Fields: pasteur-03681917