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

Year: 2024

Type: article

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.

Source: Discover Medicine

DOI: 10.1007/s44337-024-00084-w