Qars1, encoding human glutaminyl-tRNA synthetase, is a gene involved in protein synthesis, specifically the ligation of glutamine to its cognate tRNAs. This process is fundamental for the accurate translation of messenger RNA into proteins, a key biological pathway in all cells [5].

Mutations in Qars1 have been associated with severe clinical phenotypes. A study reported three patients with compound heterozygous variations in Qars1, presenting a syndrome of severe global developmental retardation, progressive microcephaly, hypotonia, mild hypoproteinemia, and diffuse brain atrophy. Their epilepsy was often refractory to many anti-epilepsy drugs [1]. Another case of a 4-year-old girl with novel compound heterozygous Qars1 variants showed orofacial dyskinesia, hand stereotypies, and focal seizures, with very mild cortical volume loss on MRI [2]. Siblings with a homozygous missense variation in Qars1 gene exon 2 had developmental epileptic encephalopathy, severe global developmental delay, and microcephaly [3]. A 6-year-old patient with compound heterozygous Qars1 variants had childhood-onset focal epilepsy, developmental delay, short stature, and an episode of steroid-responsive acute para-infectious encephalopathy [4].

In conclusion, Qars1 is essential for normal protein synthesis. Genetic studies on patients with Qars1 mutations have revealed its crucial role in preventing severe neurological disorders such as developmental epileptic encephalopathy, early-onset refractory epilepsy, and associated neurodevelopmental deficits. Understanding Qars1 function through these patient-based genetic models can potentially guide the development of targeted therapies for these rare and debilitating conditions.