title: Mitochondrial pathology in inclusion body myositis.
abstract: Inclusion body myositis (IBM) is usually associated with a large number of cytochrome c oxidase (COX)-deficient muscle fibers and acquired mitochondrial DNA (mtDNA) deletions. We studied the number of COX-deficient fibers and the amount of mtDNA deletions, and if variants in nuclear genes involved in mtDNA maintenance may contribute to the occurrence of mtDNA deletions in IBM muscle. Twenty-six IBM patients were included. COX-deficient fibers were assayed by morphometry and mtDNA deletions by qPCR. POLG was analyzed in all patients by Sanger sequencing and C10orf2 (Twinkle), DNA2, MGME1, OPA1, POLG2, RRM2B, SLC25A4 and TYMP in six patients by next generation sequencing. Patients with many COX-deficient muscle fibers had a significantly higher proportion of mtDNA deletions than patients with few COX-deficient fibers. We found previously unreported variants in POLG and C10orf2 and IBM patients had a significantly higher frequency of an RRM2B variant than controls. POLG variants appeared more common in IBM patients with many COX-deficient fibers, but the difference was not statistically significant. We conclude that COX-deficient fibers in inclusion body myositis are associated with multiple mtDNA deletions. In IBM patients we found novel and also previously reported variants in genes of importance for mtDNA maintenance that warrants further studies.
authors: Department of Pathology, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors: Ulrika
authors: U
authors: Lindgren
authors: Department of Pathology, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors: Sara
authors: S
authors: Roos
authors: Department of Pathology, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors: Carola
authors: C
authors: Hedberg Oldfors
authors: Department of Pathology, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
authors: Ali-Reza
authors: AR
authors: Moslemi
authors: Neuromuscular Center, Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors: Christopher
authors: C
authors: Lindberg
authors: Department of Pathology, Institute of Biomedicine, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. Electronic address: anders.oldfors@gu.se.
authors: Anders
authors: A
authors: Oldfors
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D048429:Cell Size; D030401:Cytochrome-c Oxidase Deficiency / Q000235:genetics / Q000473:pathology; D004265:DNA Helicases / Q000235:genetics; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics; D018485:Muscle Fibers, Skeletal / Q000473:pathology*; D018979:Myositis, Inclusion Body / Q000235:genetics* / Q000473:pathology*; D017384:Sequence Deletion
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human; D004265:DNA Helicases; C431576:TWNK protein, human
keywords: Cytochrome c oxidase deficiency; Inclusion body myositis; Mitochondrial DNA; mtDNA