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Lethal Neonatal Progression of Fetal Cardiomegaly Associated to ACAD9 Deficiency

  • Jennifer Lagoutte-Renosi
  • Isabelle Ségalas-Milazzo
  • Marie Crahes
  • Florian Renosi
  • Laurence Menu-Bouaouiche
  • Stéphanie Torre
  • Caroline Lardennois
  • Marlène Rio
  • Stéphane Marret
  • Carole Brasse-Lagnel
  • Annie Laquerrière
  • Soumeya BekriEmail author
Case Report
Part of the JIMD Reports book series (JIMD, volume 28)

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

ACAD9 Fetal cardiomegaly Mitochondrial respiratory chain β-Oxidation 

Supplementary material

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Jennifer Lagoutte-Renosi
    • 1
  • Isabelle Ségalas-Milazzo
    • 2
  • Marie Crahes
    • 3
  • Florian Renosi
    • 1
  • Laurence Menu-Bouaouiche
    • 4
  • Stéphanie Torre
    • 5
    • 6
  • Caroline Lardennois
    • 6
  • Marlène Rio
    • 7
  • Stéphane Marret
    • 5
    • 6
  • Carole Brasse-Lagnel
    • 1
    • 5
  • Annie Laquerrière
    • 3
    • 5
  • Soumeya Bekri
    • 1
    • 5
    Email author
  1. 1.Department of Metabolic BiochemistryRouen University HospitalRouenFrance
  2. 2.UMR 6014 CNRS COBRA, IRCOF, Normandie Université, Institute of Research for Innovation in Biomedicine, University of RouenMont-Saint-AignanFrance
  3. 3.Pathology LaboratoryRouen University HospitalRouenFrance
  4. 4.Glyco-MEV EA 4358, Normandie Université, Institute of Research for Innovation in Biomedicine, University of RouenMont-Saint-AignanFrance
  5. 5.NeoVasc Region-Inserm Team ERI28, Laboratory of Microvascular Endothelium and Neonate Brain LesionsInstitute of Research for Innovation in Biomedicine, University of RouenRouenFrance
  6. 6.Department of NeonatologyRouen University HospitalRouenFrance
  7. 7.Department of Pediatrics and GeneticsHôpital Necker-Enfants MaladesParisFrance

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