Analysis of mtDNA deletions in muscle by in situ hybridization

We compared the distribution of deleted mitochondrial DNA (Delta-mtDNA) In skeletal muscle of a patient with autosomal recessive (AR) and another with autosomal dominant (AD) progressive external ophthalmoplegia (PEO) by in s itu hybridization (ISH). The patients studied had similar numbers of fibers deficient in cytochrome c oxidase (COX) activity (13.6% and 12.8%) and fib ers with mitochondrial proliferation (5.5% and 5.3%). ISH suggested that ea ch COX-deficient fiber contained a single species of Delta-mtDNA. Most dele tions ablated the region between the genes encoding adenosine triphosphate (ATP) synthase subunit 8 and cytochrome b. Fibers that appeared to be deple ted of mtDNA were also present. We conclude that muscle from patients with autosomally inherited PEO contains not only Delta-mtDNA but also focal depl etion of mtDNA and that the distribution of these mtDNA defects appears to be similar. These changes most likely represent the common consequence of w hatever genetic factors are responsible for the generation of Delta-mtDNA. (C) 2000 John Wiley & Sons, Inc.