Details

Autor(en) / Beteiligte

• Scheper, Gert C
• Bugiani, Marianna
• Florentz, Catherine
• Van Coster, Rudy
• Smet, Joél
• Schiffmann, Raphael
• van Berkel, Carola G M
• Muravina, Tatjana I
• van der Klok, Thom
• Smeitink, Jan A M
• Pronk, Jan C
• van Andel, Rob J
• Uziel, Graziella
• Krägeloh-Mann, Ingeborg
• Sissler, Marie
• Serkov, Sergey V
• van der Knaap, Marjo S

Titel

Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation

Ist Teil von

• Nature genetics, 2007-04, Vol.39 (4), p.534-539

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2007

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.