As mitochondrial ARSs are key components of the mitochondrial translation apparatus, we investigated the effects of DARS2 mutations on mitochondrial functions and mitochondrial morphology in an LBSL patient.
We also report that novel mutations in mt-AspRS and mt-ArgRS genes from individuals with LBSL and PCH6, respectively, had no significant impact on the mitochondrial localizations of mt-AspRS and mt-ArgRS.
Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL, OMIM #611105) is a genetic disease of the central nervous system characterized by lower limb spasticity, cerebellar ataxia and involvement of the dorsal column.
In contrast, myelin-producing cells seem to be resistant to cell death induced by DARS2 depletion despite robust respiratory chain deficiency arguing that LBSL might originate from the primary neuronal and axonal defect.
Mutations in the DARS2 gene are known to cause leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL), a rare autosomal recessive neurological disorder.
Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation is a disorder caused by recessive mutations in the gene DARS2, which encodes mitochondrial aspartyl-tRNA synthetase.
A case with leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate (LBSL) with Its Characteristic Clinical and Neuroimaging Findings.
Impaired information-processing speed and working memory in leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate (LBSL) and DARS2 mutations: a report of three adult patients.
More recently, leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) has been reported to be caused by autosomal recessive mutations in a mitochondrial aspartyl-tRNA synthetase, DARS2 gene.
Patients with DARS2 mutations more often had involvement of structures typically affected in LBSL, including decussatio of the medial lemniscus, anterior spinocerebellar tracts, and superior and inferior cerebellar peduncles.
All eight LBSL patients were compound heterozygotes for DARS2 mutations: all carried R76SfsX5 change, seven had M134_K165del, and one had C152F change.
All eight LBSL patients were compound heterozygotes for DARS2 mutations: all carried R76SfsX5 change, seven had M134_K165del, and one had C152F change.