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* Corresponding author 1 Equipe neurogénétique et neurométabolomique Imagerie et cerveau 2 Equipe neurogénétique et neurométabolomique Imagerie et cerveau, PPF -Analyses des Systèmes Biologiques- 3 Equipe Autisme Imagerie et cerveau 4 PPF -Analyses des Systèmes Biologiques- 5 CHU de Montpellier

Abstract : Autism Spectrum Disorders ASD are a group of developmental disorders caused by environmental and genetic factors. Diagnosis is based on behavioral and developmental signs detected before 3 years of age with no reliable biological marker. The purpose of this study was to evaluate the potential use of a 2D NMR-based approach to express the global biochemical signature of autistic individuals compared to normal controls. This technique has greater spectral resolution than to 1D 1H NMR spectroscopy, which is limited by overlapping signals. The urinary metabolic profiles of 30 autistic and 28 matched healthy children were obtained using a 1H-13C NMR-based approach. The data acquired were processed by multivariate orthogonal partial least-squares discriminant analysis OPLS-DA. Some discriminating metabolites were identified: β-alanine, glycine, taurine and succinate concentrations were significatively higher, and creatine and 3-methylhistidine concentrations were lower in autistic children than in controls. We also noted differences in several other metabolites that were unidentified but characterized by a cross peak correlation in 1H-13C HSQC. Statistical models of 1H and 1H-13C analyses were compared and only 2D spectra allowed the characterization of statistically relevant changes R2Ycum=0.78 and Q2cum=0.60 in the low abundance metabolites. This method has the potential to contribute to the diagnosis of neurodevelopment disorders but needs to be validated on larger cohorts and on other developmental disorders to define its specificity.

Keywords : HSQC NMR spectroscopy Autism spectrum disorders Urinary metabolites OPLS- DA Metabolomics

Autor: Sylvie Mavel - Lydie Nadal-Desbarats - Hélène Blasco - Frédérique Bonnet-Brilhault - Catherine Barthélémy - Frédéric Mont

Fuente: https://hal.archives-ouvertes.fr/


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