Autosomal dominant progressive external ophthalmoplegia: distribution of multiple mitochondrial DNA deletions.
OBJECTIVE
To relate signs and symptoms to morphologic changes and presence of multiple mitochondrial DNA (mtDNA) deletions in a patient with autosomal dominant progressive external ophthalmoplegia (adPEO) and mitochondrial myopathy.


BACKGROUND
An etiologic association between the somatic multiple mtDNA deletions in adPEO and clinical manifestations other than the myopathy has so far not been demonstrated.


METHODS
The authors investigated a patient with adPEO and multiorgan system manifestations including levodopa-responsive parkinsonism. She died at age 61 years of pancreatic carcinoma. Autopsy tissue specimens were investigated for morphologic alterations and occurrence of mtDNA deletions by Southern blot and long-extension PCR analyses.


RESULTS
The patient had carcinoma of the pancreas with metastases to liver, lymph nodes, and bone marrow. The brain revealed slight gliosis of the gray and white matter and degeneration of the substantia nigra. The myocardium showed focal areas with loss and atrophy of myocytes and fibrosis. Analysis of mtDNA revealed multiple deletions in different regions of the brain, skeletal muscle, and myocardium. Twenty-five different mtDNA deletions were identified. Most of these were flanked by large direct-sequence repeats. Six identical deletions were found in muscle and brain.


CONCLUSIONS
These findings indicate that somatic multiple mtDNA deletions are associated with degenerative tissue changes and clinical manifestations in adPEO.
Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden.
A R
AR
Moslemi
A
A
Melberg
E
E
Holme
A
A
Oldfors
D000978:Antiparkinson Agents / Q000627:therapeutic use; D001921:Brain / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D017246:Ophthalmoplegia, Chronic Progressive External / Q000235:genetics* / Q000473:pathology*; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion
D000978:Antiparkinson Agents; D004272:DNA, Mitochondrial; D007980:Levodopa