VARS1 mutations associated with neurodevelopmental disorder are located on a short amino acid stretch of the anticodon-binding domain.

ABSTRACT: Majority of 37 human aminoacyl tRNA synthetases have been incriminated in diverse, mostly recessive, genetic diseases. In accordance with this, we uncovered a novel homozygous valyl-tRNA synthetase 1 (VARS1) gene variant, leading to p.T1068M mutation. As in the previously reported VARS1 mutations, the affected individual harboring p.T1068M was experiencing a neurodevelopmental disorder with intractable seizures, psychomotor retardation, and microcephaly. To link this phenotypic outcome with the observed genotype, we structurally modeled human VARS1 and interpreted p.T1068M within the spatial distribution of previously reported VARS1 variants. As a result, we uncovered that p.T1068M is clustered with three other pathogenic mutations in a 15 amino acid long stretc

SUBMITTER: Hiz S 

PROVIDER: S-EPMC10388123 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature