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

Paul Bastard, Kuang Chih Hsiao, Qian Zhang, Jeremy Choin, Emma Best, Jie Chen, Adrian Gervais, Lucy Bizien, Marie Materna, Christine Harmant, Maguelonne Roux, Nicola L. Hawley, Daniel E. Weeks, Stephen T. McGarvey, Karla Sandoval, Carmina Barberena-Jonas, Consuelo D. Quinto-Cortes, Erika Hagelberg, Alexander J. Mentzer, Kathryn RobsonBoubacar Coulibaly, Yoann Seeleuthner, Benedetta Bigio, Zhi Li, Gilles Uze, Sandra Pellegrini, Lazaro Lorenzo, Zineb Sbihi, Sylvain Latour, Marianne Besnard, Tiphaine Adam De Beaumais, Evelyne Jacqz Aigrain, Vivien BeZiat, Ranjan Deka, Litara Esera Tulifau, Satupa‘Itea Viali, Muagututi‘A Sefuiva Reupena, Take Naseri, Peter McNaughton, Vanessa Sarkozy, Jane Peake, Annaliesse Blincoe, Sarah Primhak, Simon Stables, Kate Gibson, See Tarn Woon, Kylie Marie Drake, Adrian V.S. Hill, Cheng Yee Chan, Richard King, Rohan Ameratunga, Iotefa Teiti, Maite Aubry, Van Mai Cao-Lormeau, Stuart G. Tangye, Shen Ying Zhang, Emmanuelle Jouanguy, Paul Gray, Laurent Abel, Andre S. Moreno-Estrada, Ryan L. Minster, Lluis Quintana-Murci, Andrew C. Wood, Jean Laurent Casanova

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    34 Citations (Scopus)

    Résumé

    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.

    langue originaleAnglais
    Numéro d'articlee20220028
    journalJournal of Experimental Medicine
    Volume219
    Numéro de publication6
    Les DOIs
    étatPublié - 6 juin 2022

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