We have recently described an autosomal dominant hereditary inclusion body 
myopathy (h-IBM). Clinically it is is characterized by congenital joint 
contractures and slowly progressive, proximal muscle weakness and 
ophthalmoplegia. There is deterioration of muscle function between 30 and 50 
years of age. While young patients show minor pathological changes in muscle, 
the middle-aged and old patients show rimmed vacuoles and inclusions of 
filaments measuring 15-18 nm in diameter. Except for the absence of significant 
inflammation the histopathology is similar to that found in sporadic inclusion 
body myositis (s-IBM). In s-IBM mitochondrial alterations including cytochrome c 
oxidase (COX) -deficient muscle fibers are common. These are due to multiple 
mitochondrial DNA (mtDNA) deletions. In this study we investigated the 
occurrence of mitochondrial alterations in autosomal dominant h-IBM. Young 
affected individuals showed no mitochondrial changes but three patients aged 38, 
51 and 59 years, respectively, showed ragged red fibers and COX-deficient muscle 
fibers. Polymerase chain reaction analysis showed multiple mtDNA deletions. By 
in situ hybridization clonal expansions of mtDNA with deletions were 
demonstrated in COX-deficient muscle fibers. Most of the analyzed deletion 
breakpoints showed nucleotide repeats flanking the deletions. The results show 
that COX-deficient muscle fibers and somatic mtDNA deletions are present in this 
family with h-IBM. The same factors may be involved in the development of mtDNA 
deletions in s-IBM and this family with h-IBM.