Pathogenic variants in glutamyl-tRNA^Gln amidotransferase subunits cause a lethal mitochondrial cardiomyopathy disorder.

ABSTRACT: Mitochondrial protein synthesis requires charging mt-tRNAs with their cognate amino acids by mitochondrial aminoacyl-tRNA synthetases, with the exception of glutaminyl mt-tRNA (mt-tRNA^Gln). mt-tRNA^Gln is indirectly charged by a transamidation reaction involving the GatCAB aminoacyl-tRNA amidotransferase complex. Defects involving the mitochondrial protein synthesis machinery cause a broad spectrum of disorders, with often fatal outcome. Here, we describe nine patients from five families with genetic defects in a GatCAB complex subunit, including QRSL1, GATB, and GATC, each showing a lethal metabolic cardiomyopathy syndrome. Functional studies reveal combined respiratory chain enzyme deficiencies and mitochondrial dysfunction. Aminoacylation of mt-tRNA^Gln an

SUBMITTER: Friederich MW 

PROVIDER: S-EPMC6170436 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature