Haploinsufficiency of PSMD12 Causes Proteasome Dysfunction and Subclinical Autoinflammation.

ABSTRACT:

Objective

Proteasome-associated autoinflammatory syndrome (PRAAS) is caused by mutations affecting components of the proteasome and activation of the type I interferon (IFN) pathway. This study was undertaken to investigate the pathogenic mechanisms of a newly recognized type of PRAAS caused by PSMD12 haploinsufficiency.

Methods

Whole-exome sequencing was performed in members of a family with skin rash, congenital uveitis, and developmental delay. We performed functional studies to assess proteasome dysfunction and inflammatory signatures in patients, and single-cell RNA sequencing to further explore the spectrum of immune cell activation.

Results

A novel truncated variant in PSMD12 (c.865C>T, p.Arg289*) was identified in 2 family members. The impairment of proteasome

SUBMITTER: Yan K 

PROVIDER: S-EPMC9321778 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature