Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy.
Brain
; 132(Pt 11): 3165-74, 2009 Nov.
Article
in En
| MEDLINE
| ID: mdl-19720722
ABSTRACT
Childhood-onset mitochondrial encephalomyopathies are usually severe, relentlessly progressive conditions that have a fatal outcome. However, a puzzling infantile disorder, long known as 'benign cytochrome c oxidase deficiency myopathy' is an exception because it shows spontaneous recovery if infants survive the first months of life. Current investigations cannot distinguish those with a good prognosis from those with terminal disease, making it very difficult to decide when to continue intensive supportive care. Here we define the principal molecular basis of the disorder by identifying a maternally inherited, homoplasmic m.14674T>C mt-tRNA(Glu) mutation in 17 patients from 12 families. Our results provide functional evidence for the pathogenicity of the mutation and show that tissue-specific mechanisms downstream of tRNA(Glu) may explain the spontaneous recovery. This study provides the rationale for a simple genetic test to identify infants with mitochondrial myopathy and good prognosis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Point Mutation
/
Mitochondrial Encephalomyopathies
/
Cytochrome-c Oxidase Deficiency
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Female
/
Humans
/
Infant
/
Male
/
Newborn
Language:
En
Journal:
Brain
Year:
2009
Type:
Article
Affiliation country:
United kingdom