A loss-of-function IFNAR1 allele in Polynesia underlies severe viral diseases in homozygotes.
A loss-of-function IFNAR1 allele in Polynesia underlies severe viral diseases in homozygotes.
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DOI：
10.1084/jem.20220028
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发表时间：
2022-06-06
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影响因子：
--
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文献类型：
--
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巴斯塔德等人。报告了一种功能丧失的 IFNAR1 变异，这种变异在西波利尼西亚血统的个体中非常常见（等位基因频率 >1%），而在其他地方则不存在或极其罕见。该等位基因的纯合子容易患严重的病毒性疾病。在全球范围内，常染色体隐性 IFNAR1 缺陷是一种罕见的先天性免疫缺陷，导致对减毒活疫苗和野生型病毒的易感性。我们报告了来自五个不相关的西波利尼西亚血统的七名儿童患有严重的病毒性疾病。所有患者都是相同无义 IFNAR1 变体 (p.Glu386*) 的纯合子。该等位基因编码一种截短的蛋白质，该蛋白质不存在于细胞表面并且丧失功能。患者的成纤维细胞对 I 型 IFN（IFN-α2、IFN-ω 或 IFN-β）没有反应。值得注意的是，这种 IFNAR1 变体在萨摩亚的次要等位基因频率 >1%，在库克岛、社会岛、马克萨斯岛和南方群岛以及斐济也观察到，而在其他测试人群（包括太平洋地区的人群）中则极其罕见或不存在。对于患有严重病毒性疾病的波利尼西亚血统个体，应考虑遗传性 IFNAR1 缺陷。
Bastard et al. report a loss-of-function IFNAR1 variant that is surprisingly common (allele frequency >1%) in individuals of western Polynesian ancestry, while it is absent or extremely rare elsewhere. Homozygotes for this allele are prone to severe viral diseases. 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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DOI：
10.1126/science.abj7965
发表时间：
2021-11-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Casanova JL;Abel L
通讯作者：
Abel L
影响因子：
30.8
作者：
Dupuis, S;Jouanguy, E;Casanova, JL
通讯作者：
Casanova, JL
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DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bastard P;Rosen LB;Zhang Q;Michailidis E;Hoffmann HH;Zhang Y;Dorgham K;Philippot Q;Rosain J;Béziat V;Manry J;Shaw E;Haljasmägi L;Peterson P;Lorenzo L;Bizien L;Trouillet-Assant S;Dobbs K;de Jesus AA;Belot A;Kallaste A;Catherinot E;Tandjaoui-Lambiotte Y;Le Pen J;Kerner G;Bigio B;Seeleuthner Y;Yang R;Bolze A;Spaan AN;Delmonte OM;Abers MS;Aiuti A;Casari G;Lampasona V;Piemonti L;Ciceri F;Bilguvar K;Lifton RP;Vasse M;Smadja DM;Migaud M;Hadjadj J;Terrier B;Duffy D;Quintana-Murci L;van de Beek D;Roussel L;Vinh DC;Tangye SG;Haerynck F;Dalmau D;Martinez-Picado J;Brodin P;Nussenzweig MC;Boisson-Dupuis S;Rodríguez-Gallego C;Vogt G;Mogensen TH;Oler AJ;Gu J;Burbelo PD;Cohen JI;Biondi A;Bettini LR;D'Angio M;Bonfanti P;Rossignol P;Mayaux J;Rieux-Laucat F;Husebye ES;Fusco F;Ursini MV;Imberti L;Sottini A;Paghera S;Quiros-Roldan E;Rossi C;Castagnoli R;Montagna D;Licari A;Marseglia GL;Duval X;Ghosn J;HGID Lab;NIAID-USUHS Immune Response to COVID Group;COVID Clinicians;COVID-STORM Clinicians;Imagine COVID Group;French COVID Cohort Study Group;Milieu Intérieur Consortium;CoV-Contact Cohort;Amsterdam UMC Covid-19 Biobank;COVID Human Genetic Effort;Tsang JS;Goldbach-Mansky R;Kisand K;Lionakis MS;Puel A;Zhang SY;Holland SM;Gorochov G;Jouanguy E;Rice CM;Cobat A;Notarangelo LD;Abel L;Su HC;Casanova JL
通讯作者：
Casanova JL
影响因子：
24.8
作者：
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通讯作者：
Casanova JL
影响因子：
64.8
作者：
Choin, Jeremy;Mendoza-Revilla, Javier;Quintana-Murci, Lluis
通讯作者：
Quintana-Murci, Lluis