A novel mitochondrial tRNAGlu (MTTE) gene mutation causing chronic progressive external ophthalmoplegia at low levels of heteroplasmy in muscle.
J Neurol Sci
; 298(1-2): 140-4, 2010 Nov 15.
Article
in En
| MEDLINE
| ID: mdl-20810132
ABSTRACT
Mitochondrial respiratory chain defects are associated with diverse clinical phenotypes in both adults and children, and may be caused by mutations in either nuclear or mitochondrial DNA (mtDNA). We report the molecular genetic investigations of a patient with chronic progressive external ophthalmoplegia (CPEO) and myopathy where muscle biopsies taken 11 years apart revealed a progressive increase in the proportion of cytochrome c oxidase (COX)-deficient fibres. Mitochondrial genetic analysis of the early biopsy had seemingly excluded both mtDNA rearrangements and mtDNA point mutations. Sequencing mtDNA from individual COX-deficient muscle fibres in the second biopsy, however, identified an unreported m.14723T>C substitution within the mitochondrial tRNAGlu (MTTE) gene, which fulfilled all canonical criteria for pathogenicity. The m.14723T>C mutation was absent from several tissues, including muscle, from maternal relatives suggesting a de novo event, whilst quantitative analysis of the first muscle biopsy confirmed a very low level of the mutation (7% mutated mtDNA), highlighting a potential problem whereby pathogenic mtDNA mutations may remain undetected using established screening methodologies.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA, Transfer, Glu
/
Ophthalmoplegia, Chronic Progressive External
/
Muscular Diseases
/
Mutation
Type of study:
Prognostic_studies
Limits:
Female
/
Humans
/
Middle aged
Language:
En
Journal:
J Neurol Sci
Year:
2010
Document type:
Article
Affiliation country:
United kingdom