Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.1.1.12 (aspartyl-tRNA synthetase)
 233 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) has recently been defined based on a highly characteristic constellation of abnormalities observed by magnetic resonance imaging and spectroscopy. LBSL is an autosomal recessive disease, most often manifesting in early childhood. Affected individuals develop slowly progressive cerebellar ataxia, spasticity and dorsal column dysfunction, sometimes with a mild cognitive deficit or decline. We performed linkage mapping with microsatellite markers in LBSL families and found a candidate region on chromosome 1, which we narrowed by means of shared haplotypes. Sequencing of genes in this candidate region uncovered mutations in DARS2, which encodes mitochondrial aspartyl-tRNA synthetase, in affected individuals from all 30 families. Enzyme activities of mutant proteins were decreased. We were surprised to find that activities of mitochondrial complexes from fibroblasts and lymphoblasts derived from affected individuals were normal, as determined by different assays.
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PMID:Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. 1738 40

Leukoencephalopathy with brainstem and spinal cord involvement and elevated brain lactate diagnosis is based on its highly characteristic pattern of abnormalities observed by magnetic resonance imaging and spectroscopy. Clinically, affected patients develop slowly progressive cerebellar ataxia, spasticity, and dorsal column dysfunction, sometimes with a mild cognitive deficit or decline. In 2007, the pathophysiology of this disorder was elucidated with the discovery of mutations in the DARS2 gene, which encodes mitochondrial aspartyl-tRNA synthetase, in affected individuals. Here, the authors present a case of leukoencephalopathy with brainstem and spinal cord involvement with normal brain lactate, in which genetic analysis revealed a new mutation in the DARS2 gene not previously described.
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PMID:Leukoencephalopathy with brainstem and spinal cord involvement and normal lactate: a new mutation in the DARS2 gene. 2050 84