title: Severe defect in mitochondrial complex I assembly with mitochondrial DNA deletions in ACAD9-deficient mild myopathy.
abstract: Acyl-coenzyme A dehydrogenase 9 (ACAD9) has a role in mitochondrial complex I (CI) assembly. Only a few patients who carry ACAD9 mutations have been reported. They mainly present with severe hypertrophic cardiomyopathy, although a minority have only mild isolated myopathy. Although the secondary factors influencing disease severity have not been elucidated, conservation of CI assembly and residual enzymatic activity have been suggested as explanations for the mild phenotypes associated with ACAD9 mutations.
  
  
  
  We report a novel homozygous ACAD9 mutation (c.1240C>T; p.Arg414Cys) in a 34-year-old woman who presented with non-progressive myopathy.
  
  
  
  We show that this ACAD9 mutation led to a severe defect in CI assembly in the patient's muscle. Furthermore, the impact of CI deficiency is confirmed by accumulation of mitochondrial DNA deletions.
  
  
  
  Our data suggest that a major defect of CI assembly is not responsible for a severe phenotype. Muscle Nerve 55: 919-922, 2017.
authors.affiliation: Nice Sophia Antipolis University, Institute for Research on Cancer and Aging (IRCAN), CNRS, INSERM, UMR 7284 and U1081, School of Medicine, 28 avenue de Valombrose, 06107, Nice cedex 2, France.|Department of Medical Genetics, National Centre for Mitochondrial Diseases, Nice Teaching Hospital, Nice, France.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Fragaki
authors.affiliation: Nice Sophia Antipolis University, Institute for Research on Cancer and Aging (IRCAN), CNRS, INSERM, UMR 7284 and U1081, School of Medicine, 28 avenue de Valombrose, 06107, Nice cedex 2, France.|Department of Medical Genetics, National Centre for Mitochondrial Diseases, Nice Teaching Hospital, Nice, France.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Chaussenot
authors.affiliation: Department of Biochemistry, Bicetre Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Paris-Sud Teaching Hospital, Paris, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Boutron
authors.affiliation: Nice Sophia Antipolis University, Institute for Research on Cancer and Aging (IRCAN), CNRS, INSERM, UMR 7284 and U1081, School of Medicine, 28 avenue de Valombrose, 06107, Nice cedex 2, France.|Department of Medical Genetics, National Centre for Mitochondrial Diseases, Nice Teaching Hospital, Nice, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bannwarth
authors.affiliation: Department of Medical Genetics, National Centre for Mitochondrial Diseases, Nice Teaching Hospital, Nice, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Cochaud
authors.affiliation: Department of Pediatrics, Nice Teaching Hospital, Nice, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Richelme
authors.affiliation: National Centre for Neuromuscular Disorders, Nice Teaching Hospital, Nice, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Sacconi
authors.affiliation: Nice Sophia Antipolis University, Institute for Research on Cancer and Aging (IRCAN), CNRS, INSERM, UMR 7284 and U1081, School of Medicine, 28 avenue de Valombrose, 06107, Nice cedex 2, France.|Department of Medical Genetics, National Centre for Mitochondrial Diseases, Nice Teaching Hospital, Nice, France.
authors.forename: Veronique
authors.initials: V
authors.lastname: Paquis-Flucklinger
mesh_terms: D044944:Acyl-CoA Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D009135:Muscular Diseases / Q000235:genetics / Q000473:pathology; D009154:Mutation / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D044944:Acyl-CoA Dehydrogenases; D042967:Electron Transport Complex I
keywords: ACAD9 mutation; complex I deficiency; complex I disassembly; exercise intolerance; mitochondrial myopathy; mtDNA deletions