This report describes developmental and epileptic encephalopathy 75, which is a subtype of developmental and epileptic encephalopathy. The human gene implicated is PARS2, which encodes prolyl-tRNA synthetase 2, mitochondrial. There is one moderate-scoring fly ortholog, Dmel\ProRS-m, for which multiple genetic reagents, including classical alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
The human gene PARS2 has not been introduced into flies.
Ubiquitous RNAi knockdown of Dmel\ProRS-m results in developmental delay and larval lethality The same phenotype is exhibited in flies bearing a homozygous null allele of Dmel\ProRS-m; larval lethality was rescued by transgenic expression of wild-type Dmel\ProRS-m. Pan-neuronal RNAi knockdown of Dmel\ProRS-m results in developmental delay during larval and pupal stages, as well as a seizure phenotype in affected adults.
[updated Aug. 2026 by FlyBase; FBrf0222196]
[DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 75; DEE75](https://omim.org/entry/618437)
[PROLYL-tRNA SYNTHETASE 2; PARS2](https://omim.org/entry/612036)
Developmental and epileptic encephalopathy-75 (DEE75) is an autosomal recessive neurodevelopmental and neurodegenerative disorder characterized by onset of severe refractory seizures in the first months of life. Patients often have global developmental delay before the onset of seizures, and thereafter achieve few milestones. EEG usually shows multifocal spikes and hypsarrhythmia, consistent with a clinical diagnosis of West syndrome. They have severely impaired intellectual development with inability to walk, absent speech, and hypotonia with axial hyperreflexia. Brain imaging shows progressive cerebral atrophy, frontal lobe atrophy, white matter abnormalities, and delayed myelination. Since the disorder is due to mitochondrial dysfunction, some patients may develop other organ involvement, including cardiomyopathy or liver and renal dysfunction. Death may occur in childhood (summary by Yin et al., 2018, pubmed:29915213). [from MIM:618437; 2026.08.25]
Developmental and epileptic encephalopathy-75 (DEE75) is caused by compound heterozygous or homozygous mutation in the PARS2 gene on chromosome 1p32. [from MIM:618437; 2026.08.25]
PARS2 is a class II amino acid tRNA synthetase, with a C-terminal active-site domain linked to an N-terminal anticodon-binding domain by a short hinge. PARS2 shares no significant similarity with its cytosolic counterpart, EPRS (MIM:138295). [from MIM:612036; 2026.08.25]
PARS2 encodes a putative member of the class II family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. This protein is encoded by the nuclear genome but is likely to be imported to the mitochondrion where it is thought to catalyze the ligation of proline to tRNA molecules. Mutations have been found in this gene in some patients with Alpers syndrome. [provided by RefSeq, Mar 2015]
One to one (1 human to 1 Drosophila); PARS2 has one high-scoring Drosophila ortholog, ProRS-m.
High-scoring ortholog of human PARS2 (1 Drosophila to 1 human).
