Abstract
ACAD9 (acyl-CoA dehydrogenase 9) is an essential factor for the mitochondrial respiratory chain complex I assembly. ACAD9, a member of acyl-CoA dehydrogenase family, has high homology with VLCAD (very long-chain acyl-CoA dehydrogenase) and harbors a homodimer structure. Recently, patients with ACAD9 deficiency have been described with a wide clinical spectrum ranging from severe lethal form to moderate form with exercise intolerance.
We report here a prenatal presentation with intrauterine growth retardation and cardiomegaly, with a fatal outcome shortly after birth. Compound heterozygous mutations, a splice-site mutation – c.1030-1G>T and a missense mutation – c.1249C>T; p.Arg417Cys, were identified in the ACAD9 gene. Their effect on protein structure and expression level was investigated. Protein modeling suggested a functional effect of the c.1030-1G>T mutation generating a non-degraded truncated protein and the p.Arg417Cys, creating an aberrant dimer. Our results underscore the crucial role of ACAD9 protein for cardiac function.
Competing interests: None declared
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Communicated by: Garry Brown
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Synopsis
A severe ACAD9 deficiency revealed by fetal cardiomegaly with a profound complex I deficiency and a partial complex V deficiency.
Author Contributions
Jennifer Lagoutte-Renosi: data interpretation and drafting the article
Isabelle Ségalas-Milazzo: protein modeling
Marie Crahes: pathological studies
Florian Renosi: data interpretation
Laurence Menu-Bouaouiche: protein modeling
Stéphanie Torre: clinical management of the patient
Caroline Lardennois: clinical management of the patient
Marlène Rio: molecular studies
Stéphane Marret: article editing
Carole Brasse-Lagnel: analysis, data interpretation, and article editing
Annie Laquerrière: interpretation of pathological findings and article editing
Soumeya Bekri: conception and design, data interpretation, and article editing
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Soumeya Bekri
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The authors have no competing interests to declare.
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Lagoutte-Renosi, J. et al. (2015). Lethal Neonatal Progression of Fetal Cardiomegaly Associated to ACAD9 Deficiency. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 28. JIMD Reports, vol 28. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_499
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DOI: https://doi.org/10.1007/8904_2015_499
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