The genetic origin of a rare mitochondrial disorder

Abstract

A pediatric patient with hypotonia, cerebellar atrophy, psychomotor delay, and increased blood‐lactate underwent whole exome sequencing. The patient harbors two novel variants of the TARS2 gene, which encodes the mitochondrial threonyl‐tRNA synthetase (mtThrRS). The aminoacylation catalyzed by mtThrRS is necessary for the translation of proteins encoded by mitochondrial DNA. One variant in the patient contains a putative splice‐site mutation, while the other variant contains a missense mutation. Both mutations are predicted to cause loss of mtThrRS function, suggesting that these novel variants of the TARS2 gene cause mitochondrial dysfunction and are therefore causal for the disorder. We aimed to assess the effects of these variants on mitochondria and energy production, and to determine the molecular effects of the TARS2 splice‐site mutation. This work contributes to the understanding of the connections between tRNA synthetase function and health.Support or Funding InformationNIH/INBRE (NIGMS) South Dakota INBRE Program (P20GM103443)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.