Pyrin variant E148Q potentiates inflammasome activation and the effect of pathogenic mutations in cis.

ABSTRACT:

Objective

The p.E148Q variant in pyrin is present in different populations at a frequency of up to 29%, and has been associated with diseases, including vasculitis and FMF. The pathogenicity of p.E148Q in FMF is unclear, even when observed in cis or in trans to a single, typically recessive, pathogenic mutation. We performed functional validation to determine whether p.E148Q increases the ability of pyrin to form an active inflammasome complex in cell lines.

Methods

We interrogated the Australian Autoinflammatory Disease RegistrY (AADRY) to find candidate inheritance patterns for the p.E148Q variant in pyrin. Different pyrin variant combinations were tested in HEK293T cells stably expressing the adaptor protein apoptosis-associated speck-like (ASC), which were analysed by fl

SUBMITTER: Reygaerts T 

PROVIDER: S-EPMC10907813 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature