AUTOIMMUNE MYOPATHIES: P.303 Mitochondrial DNA rearrangements and point mutations in inclusion body myositis

Abstract

Inclusion body myositis (IBM) is characterized by inflammatory cell infiltration, rimmed vacuoles and frequent cytochrome c oxidase (COX) deficient muscle fibers. Clonal expansion of large-scale mitochondrial DNA (mtDNA) deletions in muscle fiber segments explains most of the COX deficiency. Previous technical limitations have prevented a detailed mapping of the mtDNA rearrangements and identification of somatic point mutations in IBM. By deep sequencing of skeletal muscle mtDNA, with a mean depth of coverage of 45,000x, we performed detailed mapping of mtDNA in 21 patients with IBM and 11 age-matched controls.