Fiche publication
Date publication
octobre 2015
Journal
JIMD reports
Auteurs
Membres identifiés du Cancéropôle Est :
Dr RENOSI Florian
Tous les auteurs :
Lagoutte-Renosi J, Ségalas-Milazzo I, Crahes M, Renosi F, Menu-Bouaouiche L, Torre S, Lardennois C, Rio M, Marret S, Brasse-Lagnel C, Laquerrière A, Bekri S
Lien Pubmed
Résumé
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.
Mots clés
ACAD9, Fetal cardiomegaly, Mitochondrial respiratory chain, β-Oxidation
Référence
JIMD Rep. 2015 10 17;28:1-10
