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Lethal Neonatal Progression of Fetal Cardiomegaly Associated to ACAD9 Deficiency

Jennifer Lagoutte-Renosi 1 Isabelle Ségalas-Milazzo 2 Marie Crahes 3 Florian Renosi 1 Laurence Menu-Bouaouiche 4 Stéphanie Torre 5 Caroline Lardennois 6 Marlène Rio 7 Stéphane Marret 5 Carole Brasse-Lagnel 1, 5 Annie Laquerriere 3, 5 Soumeya Bekri 8, 5
1 Laboratoire de biochimie générale [Rouen]
2 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse
3 Service d'Anatomie et Cytologie Pathologique [CHU Rouen]
4 Glyco-MEV - Laboratoire de Glycobiologie et Matrice Extracellulaire Végétale
5 Néovasc - Endothélium microcirculatoire cérébral et lésions du système nerveux central au cours du développement
6 CHU Rouen
7 Service de Génétique Médicale [CHU Necker]
8 UNIROUEN - Université de Rouen Normandie
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.
Keywords : β-Oxidation ACAD9 Fetal cardiomegaly Mitochondrial respiratory chain
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https://hal-normandie-univ.archives-ouvertes.fr/hal-02046219
Contributor : Madeleine Roux-Merlin <>
Submitted on : Friday, February 22, 2019 - 3:36:52 PM
Last modification on : Thursday, May 27, 2021 - 5:08:04 PM

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COMUE-NORMANDIE | CNRS | INSA-ROUEN | UNIROUEN | COBRA | INC-CNRS | INSA-GROUPE | GLYCOMEV | ENSICAEN | UNILEHAVRE | UNICAEN

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Jennifer Lagoutte-Renosi, Isabelle Ségalas-Milazzo, Marie Crahes, Florian Renosi, Laurence Menu-Bouaouiche, et al.. Lethal Neonatal Progression of Fetal Cardiomegaly Associated to ACAD9 Deficiency. Journal of Inherited Metabolic Disease, Springer Verlag, 2016, 28, pp.1-10. ⟨10.1007/8904_2015_499⟩. ⟨hal-02046219⟩

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