Qars1-flox Mouse

Qars1, encoding human glutaminyl-tRNA synthetase, is responsible for the ligation of glutamine to its cognate tRNAs, which is crucial for protein synthesis. It is also a component of the multi-tRNA synthetase complex (MSC) in humans [5].

Mutations in Qars1 have been associated with severe phenotypes. Reported cases show that individuals with Qars1 gene variations often present a syndrome characterized by microcephaly, cerebral atrophy, intractable early-onset epileptic encephalopathy, global developmental retardation, and severe muscle hypotonia. Epilepsy caused by Qars1 variants is usually drug-resistant. For example, in a study of three Chinese patients, all had compound heterozygous variations in Qars1 and presented with the above-mentioned symptoms, and most had poor seizure control with common anti-epilepsy drugs [1]. Another case of a 4-year-old girl with novel Qars1 variants showed a milder neurological phenotype, but still had orofacial dyskinesia, hand stereotypies, and focal seizures [2]. A pair of siblings with a homozygous missense variation in Qars1 gene exon 2 had severe global developmental delay, microcephaly, and refractory epilepsy [3]. A 6-year-old patient with compound heterozygous Qars1 variants had childhood-onset focal epilepsy and an episode of steroid-responsive acute para-infectious encephalopathy [4].

In conclusion, Qars1 is essential for protein synthesis through its role in glutaminyl-tRNA ligation. Research on Qars1-related genetic mutations in patients has revealed its crucial role in preventing the development of severe neurological disorders, especially those involving early-onset epileptic encephalopathy, developmental retardation, and microcephaly [1,2,3,4].