Epileptic encephalopathies (EEs) encompass a large, heterogenous group of early-onset neurodevelopmental disorders characterized by intractable seizures and electroencephalogram abnormalities (reviewed in refs. 52,53). In both patients harboring the DALRD3 mutation, the onset of seizures occurred early in infancy at 6 to 7 months of age indicative of early-onset epileptic encephalopathy (Table 1). While the epilepsy of patient 2 could be controlled by anti-epileptic medications, the seizures in patient 1 were poorly controlled by medication. In addition to developmental delay and epilepsy, both patients exhibited a range of neurological and physiological symptoms consisting of severe motor and speech phenotypes, hypotonia and facial dysmorphia (Table 1). Based upon the constellation of symptoms characterized by the co-occurrence of developmental delay and frequent epileptic activity, both patients match clinical conditions now classified as developmental and epileptic encephalopathy54. Altogether, these findings identify human individuals who lack m3C modification in arginine tRNAs and reveal a biological link between m3C tRNA modification and proper neurological function.Table 1Clinical phenotype and molecular findings for patients with homozygous variants in DALRD3.Patient 1Patient 2ID19DG050919DG0510GenderMaleFemaleDate of birth17/04/200905/01/2013GenotypeNM_001276405.1:c.1251 C > A:NM_001276405.1:c.1251 C >
