A loss-of-function IFNAR1 allele in Polynesia underlies severe viral diseases in homozygotes.
J Exp Med
; 219(6)2022 06 06.
Article
em En
| MEDLINE
| ID: mdl-35442418
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-ß). 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Viroses
/
Receptor de Interferon alfa e beta
Limite:
Child
/
Humans
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
França