In Genetics in Medicine, researchers from the Medical University of Innsbruck and other international centers consider TRMU gene variants that can lead to reversible acute liver failure in infants, along with the phenotypic characteristics accompanying these alterations. The TRMU gene codes for a methyltransferase enzyme that modifies mitochondrial transfer RNAs during the mitochondrial translation process, the team explains, and past research suggests that pathogenic variants affecting both copies of the gene can lead to TRMU deficiency, acute liver failure, and sometimes death. Across 62 TRMU-deficient patients from 56 families, the authors used targeted sequencing and variant pathogenicity modeling in silico to track down four dozen pathogenic or likely pathogenic variants. The authors note that acute liver failure stemming from these alterations was reversible in 65 percent of the individuals profiled over a median follow up time of almost four years, particularly with the use of cysteine supplements. Even so, the condition was deadly in more than one-third of those affected, with loss-of-function variation in TRMU portending poorer survival patterns. "TRMU deficiency is predominantly a disease of the first year of life," they explain, noting that neurodevelopmental delay was detected in a subset of patients over the study's follow up time.
Researchers Characterize Pathogenic Variants in Acute Liver Failure-Related Gene
Nov 01, 2022