Nucleus-driven multiple large-scale deletions of the human mitochondrial genome: a new autosomal dominant disease.

摘要: We studied several affected and one nonaffected individuals belonging to three unrelated pedigrees. The pathological trait was an autosomal dominant mitochondrial myopathy due large-scale multiple deletions of the genome. Clinically, symptomatic patients had progressive external ophthalmoplegia, muscle weakness wasting, sensorineural hypoacusia, and, in some cases, vestibular areflexia tremor. biopsies all examined showed ragged-red fibers, neurogenic changes, a partially decreased histochemical reaction cytochrome c oxidase. Multiple mtDNA heteroplasmy detected by both Southern blot analysis PCR amplification, whereas unaffected individual normal homoplasmic hybridization pattern. These findings confirm add further details existence new human disease--defined clinically as myopathy, genetically Mendelian trait, molecularly accumulation multiple, genome--that is impaired nuclear control during replication.