Type I Interferonopathy due to a Homozygous Loss-of-Inhibitory Function Mutation in STAT2.

ABSTRACT:

Purpose

STAT2 is both an effector and negative regulator of type I interferon (IFN-I) signalling. We describe the characterization of a novel homozygous missense STAT2 substitution in a patient with a type I interferonopathy.

Methods

Whole-genome sequencing (WGS) was used to identify the genetic basis of disease in a patient with features of enhanced IFN-I signalling. After stable lentiviral reconstitution of STAT2-null human fibrosarcoma U6A cells with STAT2 wild type or p.(A219V), we performed quantitative polymerase chain reaction, western blotting, immunofluorescence, and co-immunoprecipitation to functionally characterize the p.(A219V) variant.

Results

WGS identified a rare homozygous single nucleotide transition in STAT2 (c.656C > T), resulting in a p.(A219V) su

SUBMITTER: Zhu G 

PROVIDER: S-EPMC10110676 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature