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Severe defect in mitochondrial complex I assembly with mitochondrial DNA deletions in ACAD9 ‐deficient mild myopathy
Author(s) -
Fragaki Konstantina,
Chaussenot Annabelle,
Boutron Audrey,
Bannwarth Sylvie,
Cochaud Charlotte,
Richelme Christian,
Sacconi Sabrina,
PaquisFlucklinger Veronique
Publication year - 2017
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.25262
Subject(s) - mitochondrial dna , myopathy , mitochondrial myopathy , mutation , phenotype , hypertrophic cardiomyopathy , biology , mitochondrion , cardiomyopathy , genetics , medicine , endocrinology , gene , heart failure
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