Severe defect in mitochondrial complex I assembly with mitochondrial DNA deletions in ACAD9-deficient mild myopathy.
INTRODUCTION
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.


METHODS
We report a novel homozygous ACAD9 mutation (c.1240C>T; p.Arg414Cys) in a 34-year-old woman who presented with non-progressive myopathy.


RESULTS
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.


CONCLUSION
Our data suggest that a major defect of CI assembly is not responsible for a severe phenotype. Muscle Nerve 55: 919-922, 2017.
['Fragaki|Konstantina|K|', 'Chaussenot|Annabelle|A|', 'Boutron|Audrey|A|', 'Bannwarth|Sylvie|S|', 'Cochaud|Charlotte|C|', 'Richelme|Christian|C|', 'Sacconi|Sabrina|S|', 'Paquis-Flucklinger|Veronique|V|']
D044944:Acyl-CoA Dehydrogenases D000328:Adult D003241:Consanguinity D004252:DNA Mutational Analysis D004272:DNA, Mitochondrial D042967:Electron Transport Complex I D005260:Female D006801:Humans D009135:Muscular Diseases D009154:Mutation
ACAD9 mutation complex I deficiency complex I disassembly exercise intolerance mitochondrial myopathy mtDNA deletions