Title :

Fluxomic evidence for impaired contribution of short-chain acyl-CoA dehydrogenase to mitochondrial palmitate beta-oxidation in symptomatic patients with ACADS gene susceptibility variants

Author(s) :

Dessein, Anne-Frédérique [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc) - U1172
Fontaine, Monique [Auteur]
Maladies RAres du DÉveloppement embryonnaire et du Métabolisme : du phénotype au génotype et à la Fonction (RADEME) - EA 7364
Joncquel, Marie [Auteur]
Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]
Briand, G. [Auteur]
Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]
Sechter, C. [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Mention, Karine [Auteur]
Hôpital Jeanne de Flandre [Lille]
Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Dobbelaere, Dries [Auteur]
Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]
Douillard, C. [Auteur]
Lacour, A. [Auteur]
Redonnet-Vernhet, I. [Auteur]
Hôpital Pellegrin
Lamireau, D. [Auteur]
Barth, M. [Auteur]
Minot-Myhié, M. C. [Auteur]
Service de Neurologie [CHU Rennes]
Kuster, A. [Auteur]
De Lonlay, P. [Auteur]
Hôpital Necker - Enfants Malades [AP-HP]
Imagine - Institut des maladies génétiques (IHU) [Imagine - U1163]
Gregersen, N. [Auteur]
Acquaviva, C. [Auteur]
Vianey-Saban, C. [Auteur]
Vamecq, Joseph [Auteur]
Maladies Rares du Développement : Génétique, Régulation et Protéomique (RADEME) - ULR 7364
Redonnet-Vernhet, I [Auteur]

Journal title :

Clinica Chimica Acta

Abbreviated title :

Clin. Chim. Acta

Volume number :

471

Pages :

101-106

Publication date :

2017-05-28

ISSN :

0009-8981

English keyword(s) :

In situ fluxomic assessment of protein function
ACADS pathogenic mutation
ACADS susceptibility variants (c.511C > T and c.625G > A)
SCAD deficiency
SCAD functional impairment
ACADS Short-chain acyl-CoA dehydrogenase [SCAD]

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Background Despite ACADS (acyl-CoA dehydrogenase, short-chain) gene susceptibility variants (c.511C > T and c.625G > A) are considered to be non-pathogenic, encoded proteins are known to exhibit altered kinetics. Whether ...
Show more >Background Despite ACADS (acyl-CoA dehydrogenase, short-chain) gene susceptibility variants (c.511C > T and c.625G > A) are considered to be non-pathogenic, encoded proteins are known to exhibit altered kinetics. Whether or not, they might affect overall fatty acid β-oxidation still remains, however, unclear. Methods De novo biosynthesis of acylcarnitines by whole blood samples incubated with deuterated palmitate (16-2H3,15-2H2-palmitate) is suitable as a fluxomic exploration to distinguish between normal and disrupted β-oxidation, abnormal profiles and ratios of acylcarnitines with different chain-lengths being indicative of the site for enzymatic blockade. Determinations in 301 control subjects of ratios between deuterated butyrylcarnitine and sum of deuterated C2 to C14 acylcarnitines served here as reference values to state specifically functional SCAD impairment in patients addressed for clinical and/or biological suspicion of a β-oxidation disorder. Results Functional SCAD impairment was found in 39 patients. The 27 patients accepting subsequent gene studies were all positive for ACADS mutations. Twenty-six of 27 patients were positive for c.625G > A variant. Twenty-three of 27 patients harbored susceptibility variants as sole ACADS alterations (18 homozygous and 3 heterozygous for c.625G > A, 2 compound heterozygous for c.625G > A/c.511C > T). Conclusion Our present fluxomic assessment of SCAD suggests a link between ACADS susceptibility variants and abnormal β-oxidation consistent with known altered kinetics of these variants.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CHU Lille

Collections :

• Maladies Rares du Développement : Génétique, Régulation et Protéomique (RADEME) - ULR 7364

Submission date :

2023-06-05T07:49:04Z
2024-02-21T14:24:47Z