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

Jean-Laurent Casanova ^{1, 2, 3, 4, 5} Andrew Wood ⁶ Lluis Quintana-Murci ^{7, 8} Ryan Minster ⁹ Andrés Moreno-Estrada ¹⁰ Laurent Abel ^{3, 1, 2, 4} Paul Gray ^{11, 12} Emmanuelle Jouanguy ^{1, 2, 3, 4} Shen-Ying Zhang ^{1, 2, 3, 4} Stuart Tangye ^{13, 14} Van-Mai Cao-Lormeau ¹⁵ Maite Aubry ¹⁵ Iotefa Teiti ¹⁵ Rohan Ameratunga ^{16, 6} Richard King ¹⁷ Cheng-Yee Chan ¹⁷ Adrian Hill ¹⁸ Kylie Drake ¹⁷ See-Tarn Woon ^{16, 6} Kate Gibson Simon Stables ¹⁶ Sarah Primhak ⁶ Annaliesse Blincoe Jane Peake ¹⁹ Vanessa Sarkozy ^{11, 12} Peter Mcnaughton ¹⁹ Take Naseri ^{20, 21} Muagututi‘a Reupena Satupa‘itea Viali Litara Esera Tulifau ²² Ranjan Deka ²³ Vivien Béziat ^{1, 4} Evelyne Jacqz Aigrain ^{24, 25} Tiphaine Adam de Beaumais ^{26, 24} Marianne Besnard ²⁷ Sylvain Latour ¹ Zineb Sbihi ¹ Lazaro Lorenzo ^{1, 4} Sandra Pellegrini ²⁸ Gilles Uzé ²⁹ Zhi Li ^{28, 7} Benedetta Bigio ² Yoann Seeleuthner ^{1, 4} Boubacar Coulibaly ^{1, 4} Kathryn Robson ¹⁸ Alexander Mentzer ¹⁸ Erika Hagelberg ³⁰ Consuelo Quinto-Cortés ³¹ Carmina Barberena-Jonas ³¹ Karla Sandoval ³¹ Stephen Mcgarvey ²⁰ Daniel Weeks ⁹ Nicola Hawley ^{32, 20} Maguelonne Roux ^{7, 33} Christine Harmant ⁷ Marie Materna ^{1, 34, 4} Lucy Bizien ^{1, 34, 4} Adrian Gervais ^{1, 34, 4} Jie Chen ^{2, 35} Emma Best ⁶ Jeremy Choin ⁷ Qian Zhang ^{34, 2, 1, 4} Kuang-Chih Hsiao ^{6, 36} Paul Bastard ^{34, 2, 1, 4}

1 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)

2 Rockefeller University [New York]

3 Equipe Inserm U1163 - Human genetics of infectious diseases: Complex predisposition

Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)

4 Département de Pédiatrie et maladies infectieuses [CHU Necker]

5 HHMI - Howard Hughes Medical Institute

6 University of Auckland [Auckland]

7 Génétique Evolutive Humaine - Human Evolutionary Genetics

8 Chaire Génomique humaine et évolution

9 PITT - University of Pittsburgh

10 CINVESTAV - Langebio

11 UNSW - University of New South Wales [Sydney]

12 Sydney Children's hospital

13 Garvan Institute of medical research

14 UNSW Faculty of Medicine [Sydney]

15 ILM - Institut Louis Malardé [Papeete]

16 Auckland City Hospital

17 Canterbury Health Laboratories

18 University of Oxford [Oxford]

19 University of Queensland [Brisbane]

20 Brown University

21 Ministry of Health [Samoa]

22 TTM - Tupua Tamasese Meaole Hospital

23 UC - University of Cincinnati

24 AP-HP - Hopital Saint-Louis [AP-HP]

25 UPCité - Université Paris Cité

26 IGR - Institut Gustave Roussy

27 Centre Hospitalier de Polynésie Française

28 Signalisation des Cytokines - Cytokine Signaling

29 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)

30 UiO - University of Oslo

31 LANGEBIO - National Laboratory of Genomics for Biodiversity

32 Yale University [New Haven]

33 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB

34 Equipe Inserm U1163 - Human genetics of infectious diseases : Mendelian predisposition

Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)

35 Shanghai Jiaotong University

36 MCRI - Murdoch Children's Research Institute

Abstract : 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.

Keywords : Human disease genetics Immunodeficiency Infectious disease and host defense Innate immunity and inflammation

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Genetics

Life Sciences [q-bio] / Human health and pathology / Infectious diseases

Complete list of metadata

https://hal-pasteur.archives-ouvertes.fr/pasteur-03681917
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Submitted on : Monday, May 30, 2022 - 3:54:37 PM
Last modification on : Thursday, October 20, 2022 - 3:10:07 PM
Long-term archiving on: : Wednesday, August 31, 2022 - 7:06:46 PM