anti-Aspartyl-tRNA Synthetase 2, Mitochondrial (DARS2) Antibodies

Mouse (Murine) Aspartyl-tRNA Synthetase 2, Mitochondrial (DARS2) interaction partners

1. Results now provide the first evidence that loss of DARS2 in neurons leads to strong mitochondrial dysfunction and progressive loss of cells.

2. DARS2 depletion in heart and skeletal muscle leads to the severe deregulation of mitochondrial protein synthesis followed by a strong respiratory chain deficit in both tissues.

Human Aspartyl-tRNA Synthetase 2, Mitochondrial (DARS2) interaction partners

1. Whole exome sequencing of the proband identified two compound heterozygous variants (NM_018122.4:c.1762C > G and c.563G > A) in DARS2

2. Results show that DARS2 is strongly upregulated in hepatocellular carcinoma (HCC) and is associated with HCC progression. DARS2 promotes HCC tumorigenesis by accelerating cell cycle progression and attenuating cell apoptosis.

3. Mutations with mild effects on solubility occur in patients as allelic combinations whereas those with strong effects on solubility or on aminoacylation are necessarily associated with a partially functional allele.

4. This study identified DARS2-associated leukoencephalopathy with hypomyelination with brainstem and spinal cord involvement and leg spasticity.

5. 60 different DARS2 mutations were identified in 78 patients with leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation, 13 of which have not been reported before

6. Cognitive impairment seems to be common among patients with leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate and DARS2 mutations

7. A comparison of biophysical properties of human mitochondrial aspartyl-tRNA synthetase, HsaDRS2, with them to those of a bacterial (E. coli) homolog, EcoDRS.

8. Pathogenic mutations causing LBSL affect mitochondrial aspartyl-tRNA synthetase in diverse way

9. We describe two new cases of Leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate with a novel pathogenic mutation in the DARS2 gene

10. Case demonstrates that DARS2 mutation homozygosity is not lethal, as suggested earlier, but compatible with a rather benign disease course.

11. Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation is associated with cell-type-dependent splicing of mtAspRS mRNA.

12. A novel homozygous mutation of DARS2 may cause a severe LBSL (Leukoencephalopathy with brain stem and spinal cord involvement with lactate elevation) variant.

13. This report describes two novel heterozygote composite mutations in the DARS2 gene

14. DARS2 mutations cause childhood-to-adolescence onset leucoencephalopathy, but they do not seem to be associated with multiple sclerosis.

15. The gene for mitochondrial aspartyl-tRNA synthetase is described and the initial characterization of the enzyme is reported. Genes for the remaining missing human synthetases have also been found with the exception of glutaminyl-tRNA synthetase.

16. Mutations in DARS2, which encodes mitochondrial aspartyl-tRNA synthetase, in affected individuals with leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation.