Aberrant tRNA processing causes an autoinflammatory syndrome responsive to TNF inhibitors.

ABSTRACT:

Objectives

To characterise the clinical features, immune manifestations and molecular mechanisms in a recently described autoinflammatory disease caused by mutations in TRNT1, a tRNA processing enzyme, and to explore the use of cytokine inhibitors in suppressing the inflammatory phenotype.

Methods

We studied nine patients with biallelic mutations in TRNT1 and the syndrome of congenital sideroblastic anaemia with immunodeficiency, fevers and developmental delay (SIFD). Genetic studies included whole exome sequencing (WES) and candidate gene screening. Patients' primary cells were used for deep RNA and tRNA sequencing, cytokine profiling, immunophenotyping, immunoblotting and electron microscopy (EM).

Results

We identified eight mutations in these nine pat

SUBMITTER: Giannelou A 

PROVIDER: S-EPMC5890629 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature