Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy: QARS1 variants associated with a severe phenotype in a patient

Abstract

Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy is a rare disease due to QARS1 pathogenic variants altering the Glutaminyl-tRNA synthetase 1 activity. We report a Tunisian child presenting with neonatal onset seizures, severe psychomotor delay, retinal abnormalities and MRI cerebral supratentorial atrophy lesions. Whole exome and Sanger sequencing revealed two compound heterozygous variants of QARS1. Three-dimensional analysis of the mutant Glutaminyl-tRNA synthetase 1 predicted altered catalytic and tRNA-binding functions. Genotype–phenotype correlations emphasize the combined effect of the zygosity and the location of the pathogenic variants within the protein domains on the severity of the disease.