DARS2 mutations in mitochondrial leucoencephalopathy and multiple sclerosis.
J Med Genet
; 47(1): 66-70, 2010 Jan.
Article
em En
| MEDLINE
| ID: mdl-19592391
ABSTRACT
BACKGROUND:
Leucoencephalopathy with brain stem and spinal cord involvement and high brain lactate (LBSL) was first defined by characteristic magnetic resonance imaging and spectroscopic findings. The clinical features include childhood or juvenile onset slowly progressive ataxia, spasticity, and dorsal column dysfunction, occasionally accompanied by learning difficulties. Mutations in DARS2, encoding mitochondrial aspartyl-tRNA synthetase, were recently shown to cause LBSL. The signs and symptoms show some overlap with the most common leucoencephalopathy of young adults, multiple sclerosis (MS).OBJECTIVE:
To clarify the molecular background of LBSL patients in Finland, and to look for DARS2 mutations in a group of MS patients.METHODS:
Clinical evaluation of LBSL patients, DARS2 sequencing and haplotype analysis, and carrier frequency determination in Finland.RESULTS:
All eight LBSL patients were compound heterozygotes for DARS2 mutations all carried R76SfsX5 change, seven had M134_K165del, and one had C152F change. Axonal neuropathy was found in five of the eight patients. The carrier frequencies of the R76SfsX5 and M134_K165del mutations were 195 and 1380, respectively. All patients shared common European haplotypes, suggestive of common European LBSL ancestors. No enrichment of the two common DARS2 mutations was found in 321 MS patients.CONCLUSION:
All LBSL patients were compound heterozygotes, which suggests that DARS2 mutation homozygosity may be lethal or manifest as a different phenotype. The authors show here that despite identical mutations the clinical picture was quite variable in the patients. Axonal neuropathy was an important feature of LBSL. DARS2 mutations cause childhood-to-adolescence onset leucoencephalopathy, but they do not seem to be associated with MS.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aspartato-tRNA Ligase
/
Doenças Mitocondriais
/
Leucoencefalopatias
/
Esclerose Múltipla
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
J Med Genet
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Finlândia