Format

Send to

Choose Destination
Arch Neurol. 2004 Feb;61(2):269-72.

Revelation of a new mitochondrial DNA mutation (G12147A) in a MELAS/MERFF phenotype.

Author information

1
First Division of Neurology, Department of Neurological Sciences, Second University of Naples, School of Medicine, Poclinico Universitario Federico II, Italy. marina.melone@unina2.it

Abstract

BACKGROUND:

A 26-year-old man presented at onset with the syndrome of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes (MELAS) and later with a phenotype for MELAS and myoclonic epilepsy and ragged red fiber disease (MELAS/MERRF).

OBJECTIVE:

To identify the possible defects in the mitochondrial genome in blood and muscle samples of the patient.

DESIGN:

Case study of a patient clinically exhibiting strokelike episodes and then epilepsy with myoclonic features, ataxia, and dementia.

SETTING:

Research unit of a university hospital.

MAIN OUTCOME MEASURES:

Electromyographic, morphologic, and biochemical studies of muscle and molecular analysis of blood and muscle to investigate mitochondrial DNA (mtDNA) size and quantity.

RESULTS:

Morphologically, we found abnormal mitochondrial proliferation with several cytochrome-c oxidase (COX)-negative fibers in muscle biopsy specimens; the analysis of serial sections showed a decreased immunoreactivity for the mtDNA-encoded subunits COXII and, partially, COXI. Biochemically, we found a partial and isolated COX deficiency. The complete mtDNA sequence analysis identified 3 sequence changes, 2 of which were reported polymorphisms. The remaining change, a G12147A transition in the transfer RNA(His) gene, appeared to be the likely pathogenic mutation.

CONCLUSIONS:

Our data propose that the G12147A change, the first mutation in the transfer RNA(His) gene associated with an overlapped MELAS/MERFF phenotype, is the cause of the encephalomyopathy in this patient interfering with the overall mitochondrial protein synthesis.

PMID:
14967777
DOI:
10.1001/archneur.61.2.269
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center