NM_018122.5(DARS2):c.1825C>T (p.Arg609Trp) AND Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation

Clinical significance:Pathogenic (Last evaluated: Oct 1, 2011)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000023848.4

Allele description [Variation Report for NM_018122.5(DARS2):c.1825C>T (p.Arg609Trp)]

NM_018122.5(DARS2):c.1825C>T (p.Arg609Trp)

Gene:
DARS2:aspartyl-tRNA synthetase 2, mitochondrial [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q25.1
Genomic location:
Preferred name:
NM_018122.5(DARS2):c.1825C>T (p.Arg609Trp)
HGVS:
  • NC_000001.11:g.173857592C>T
  • NG_016138.1:g.37934C>T
  • NM_018122.5:c.1825C>T
  • NP_060592.2:p.Arg609Trp
  • NC_000001.10:g.173826730C>T
  • NM_018122.4:c.1825C>T
Protein change:
R609W; ARG609TRP
Links:
OMIM: 610956.0013; dbSNP: rs200670286
NCBI 1000 Genomes Browser:
rs200670286
Molecular consequence:
  • NM_018122.5:c.1825C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Leukoencephalopathy with Brainstem and Spinal Cord Involvement and Lactate Elevation (LBSL)
Synonyms:
MITOCHONDRIAL ASPARTYL-tRNA SYNTHETASE DEFICIENCY; LEUKOENCEPHALOPATHY WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LACTATE ELEVATION, MILD; Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation
Identifiers:
MedGen: C1970180; Orphanet: 137898; OMIM: 611105

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000045139OMIMno assertion criteria providedPathogenic
(Oct 1, 2011)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Acetazolamide-responsive exercise-induced episodic ataxia associated with a novel homozygous DARS2 mutation.

Synofzik M, Schicks J, Lindig T, Biskup S, Schmidt T, Hansel J, Lehmann-Horn F, Schöls L.

J Med Genet. 2011 Oct;48(10):713-5. doi: 10.1136/jmg.2011.090282. Epub 2011 Jul 11.

PubMed [citation]
PMID:
21749991

Details of each submission

From OMIM, SCV000045139.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a 25-year-old German woman with a mild form of leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL; 611105), Synofzik et al. (2011) identified a homozygous 1825C-T transition in exon 17 of the DARS2 gene, resulting in an arg609-to-trp (R609W) substitution in a highly conserved residue in mammals. Each unaffected parent was heterozygous for the mutation, which was not found in 338 controls. Functional analysis was not performed. She presented with paroxysmal exercise-induced gait ataxia that first occurred up to 5 times a day and lasted for a few seconds to 5 minutes, but increased in frequency over a few years. Other features included mild distal deficits in position and vibration sense, mild leg spasticity, and hyperreflexia, but she never had permanent cerebellar ataxia or gait spasticity. Serum lactate was intermittently increased, and brain MRI showed T2 hyperintense lesions in the cerebellar white matter, deep cerebral white matter, and periventricular region, with some involvement of the pyramidal tracts and dorsal columns. Treatment with acetazolamide resulted in significantly decreased frequency of the attacks. The findings indicated that this disorder can have a milder phenotype and even present with episodic ataxia.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 30, 2019

Support Center