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8 results on '"Centre de Biologie et Pathologie Est (CBPE)"'

1. The PPARγ pathway determines electrophysiological remodelling and arrhythmia risks in DSC2 arrhythmogenic cardiomyopathy

Author

Jean‐Baptiste Reisqs, Adrien Moreau, Azzouz Charrabi, Yvonne Sleiman, Albano C. Meli, Gilles Millat, Veronique Briand, Philippe Beauverger, Sylvain Richard, Philippe Chevalier, Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sanofi Aventis R&D [Chilly-Mazarin], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Hospices Civils de Lyon (HCL), Centre de Biologie et Pathologie Est (CBPE), Hospices Civils de Lyon (HCL)-Centre National de Référence des Légionelles, and MORNET, Dominique

Subjects
[SDV] Life Sciences [q-bio], Desmocollins, PPAR gamma, [SDV]Life Sciences [q-bio], Molecular Medicine, Medicine (miscellaneous), Humans, Arrhythmias, Cardiac, Cardiac Electrophysiology, ComputingMilieux_MISCELLANEOUS, Arrhythmogenic Right Ventricular Dysplasia
Abstract

International audience; No abstract available

Published
2021

2. A National French consensus on gene lists for the diagnosis of myopathies using next-generation sequencing

Author

Céline Bouchet-Séraphin, John Rendu, Cécile Acquaviva-Bourdain, Mathieu Cerino, Aurélien Perrin, Frédérique Audic, Jon Andoni Urtizberea, Julien Fauré, Roseline Froissart, Mireille Cossée, Martin Krahn, Corinne Metay, Laurence Michel-Calemard, Damien Sternberg, Judith Melki, Jean Pouget, Emmanuelle Campana-Salort, Nathalie Seta, Annamaria Molon, Juliette Nectoux, François Petit, Valérie Biancalana, Brigitte Chabrol, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de biologie et pathologie Est, Hospices Civils de Lyon (HCL), Service de biochimie et de génétique moléculaire [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal [CHU Lyon] (Centre de Biologie et Pathologie Est), Hospices Civils de Lyon (HCL)-Groupement Hospitalier Est, Hôpital de la Timone [CHU - APHM] (TIMONE), Filière Neuromusculaire (FILNEMUS), Service de Neurologie Pédiatrique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de référence des maladies neuromusculaires et de la SLA, Centre de Biologie et Pathologie Est (CBPE), Hospices Civils de Lyon (HCL)-Centre National de Référence des Légionelles, Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Laboratoire de biochimie et génétique moléculaire, CHU Grenoble, Service de Biochimie-Génétique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Biochimie Métabolique et Cellulaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Pitié-Salpêtrière [AP-HP], Astrophysique Interprétation Modélisation (AIM (UMR_7158 / UMR_E_9005 / UM_112)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Astrophysique Interprétation Modélisation (AIM (UMR7158 / UMR_E_9005 / UM_112))

Subjects
Consensus, [SDV]Life Sciences [q-bio], MEDLINE, Computational biology, Biology, DNA sequencing, Article, 03 medical and health sciences, Gene panel, Genetics, Humans, Genetic Testing, Gene, Genetics (clinical), Societies, Medical, 0303 health sciences, Genetic heterogeneity, 030305 genetics & heredity, Neuromuscular Diseases, Sequence Analysis, DNA, Diagnostic strategy, 3. Good health, Practice Guidelines as Topic, France, Genetic diagnosis, Core gene
Abstract

International audience; Next-generation sequencing (NGS) gene-panel-based analyses constitute diagnosis strategies which are adapted to the genetic heterogeneity within the field of myopathies, including more than 200 implicated genes to date. Nonetheless, important inter-laboratory diversity of gene panels exists at national and international levels, complicating the exchange of data and the visibility of the diagnostic offers available for referring neurologists. To address this issue, we here describe the initiative of the genetic diagnosis section of the French National Network for Rare Neuromuscular Diseases (Filière Nationale des Maladies Rares Neuromusculaires, FILNEMUS), which led to set up a consensual nationwide diagnostic strategy among the nine French genetic diagnosis laboratories using NGS for myopathies. The strategy is based on the determination of 13 clinical and/or histological entry-diagnosis groups, and consists for each group either in a successive NGS analysis of a "core gene list" followed in case of a negative result by the analysis of an "exhaustive gene list", or in the NGS analysis of a "unique exhaustive gene list".

Published
2019

3. Intra-monocyte Pharmacokinetics of Imiglucerase Supports a Possible Personalized Management of Gaucher Disease Type 1

Author

Juliette Berger, Marie Vigan, Bruno Pereira, Thu Thuy Nguyen, Roseline Froissart, Nadia Belmatoug, Florence Dalbiès, Agathe Masseau, Christian Rose, Christine Serratrice, Yves-Marie Pers, Ivan Bertchansky, Fabrice Camou, Monia Bengherbia, Céline Bourgne, Catherine Caillaud, Magali Pettazzoni, Amina Berrahal, Jérôme Stirnemann, France Mentré, Marc G. Berger, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias - Clermont Auvergne (CHELTER), Université Clermont Auvergne (UCA), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), service de Biostatistiques, DRCI, Centre Hospitalier Universitaire de Clermont-Ferrand, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Centre de Biologie et Pathologie Est (CBPE), Hospices Civils de Lyon (HCL)-Centre National de Référence des Légionelles, Hôpitaux Universitaires Paris Nord Val de Seine, CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Médecine Interne [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital St-André, Réanimation, CHU Bordeaux [Bordeaux], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Service de biochimie métabolique [CHU Necker], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital Universitaire de Genève, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), CHU Clermont-Ferrand, Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Claude Huriez [Lille], CHU Lille, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
0301 basic medicine, Oncology, Male, [SDV]Life Sciences [q-bio], Disease, Glucosylceramidase/metabolism/pharmacokinetics/therapeutic use, Monocytes, 0302 clinical medicine, Monocytes/metabolism, Medicine, Pharmacology (medical), Precision Medicine, Child, ComputingMilieux_MISCELLANEOUS, ddc:616, Aged, 80 and over, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Enzyme replacement therapy, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Cohort, Glucosylceramidase, Female, medicine.drug, Adult, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Imiglucerase, Adolescent, Models, Biological, Gaucher Disease/drug therapy/metabolism, 03 medical and health sciences, Young Adult, Pharmacotherapy, Pharmacokinetics, Internal medicine, Humans, Enzyme Replacement Therapy, Aged, Pharmacology, Gaucher Disease, business.industry, nutritional and metabolic diseases, Confidence interval, 030104 developmental biology, ddc:618.97, business, Glucocerebrosidase, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Intravenous imiglucerase enzyme replacement therapy for Gaucher disease type 1 administered every 2 weeks is at variance with the imiglucerase plasma half-life of a few minutes. We hypothesized that studying the pharmacokinetics of imiglucerase in blood Gaucher disease type 1 monocytes would be more relevant for understanding enzyme replacement therapy responses. Glucocerebrosidase intra-monocyte activity was studied by flow cytometry. The pharmacokinetics of imiglucerase was analyzed using a population-pharmacokinetic model from a cohort of 31 patients with Gaucher disease type 1 who either started or were receiving long-term treatment with imiglucerase. A pharmacokinetic analysis of imiglucerase showed a two-compartment model with a high peak followed by a two-phase exponential decay (fast phase half-life: 0.36 days; slow phase half-life: 9.7 days) leading to a median 1.4-fold increase in glucocerebrosidase intra-monocyte activity from the pre-treatment activity (p = 0.04). In patients receiving long-term treatment, for whom the imiglucerase dose per infusion was chosen on the basis of disease aggressiveness/response, imiglucerase clearance correlated with the administered dose. However, the residual glucocerebrosidase intra-monocyte activity value was dose independent, suggesting that the maintenance of imiglucerase residual activity is patient specific. Endogenous pre-treatment glucocerebrosidase intra-monocyte activity was the most informative single parameter for distinguishing patients without (n = 10) and with a clinical indication (n = 17) for starting enzyme replacement therapy (area under the receiver operating characteristic curve: 0.912; 95% confidence interval 0.8–1; p

Published
2019

4. Analysis of Mucopolysaccharidosis Type VI through Integrative Functional Metabolomics

Author

Stéphane Marret, Monique Piraud, Carine Pilon, Tony Pereira, Soumeya Bekri, Abdellah Tebani, Lenaig Abily-Donval, Farid Zerimech, Isabelle Schmitz-Afonso, Jérôme Ausseil, Carlos Afonso, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Endothélium microcirculatoire cérébral et lésions du système nerveux central au cours du développement (Néovasc), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Team 4 'NeoVasc' - INSERM U1245, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre de Biologie et Pathologie Est (CBPE), Hospices Civils de Lyon (HCL)-Centre National de Référence des Légionelles, CHU Amiens-Picardie, Laboratoire de Biochimie et Biologie Moléculaire [CHRU Lille] (Pôle de Biologie Pathologie Génétique), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biochimie générale [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre hospitalier universitaire de Rouen, CHU Lille, Institut Pasteur de Lille, Université de Lille, Université de Rouen Normandie [UNIROUEN], Chimie Organique et Bioorganique : Réactivité et Analyse [COBRA], Service de Biochimie et Biologie Moléculaire Grand Est [HCL, Lyon] [Centre de Biologie et de Pathologie], IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483, and Service de pédiatrie néonatale et réanimation - neuropédiatrie [CHU Rouen]

Subjects
Arylsulfatase B, Male, [SDV]Life Sciences [q-bio], Mucopolysaccharidosis type VI, Tandem mass spectrometry, lcsh:Chemistry, 0302 clinical medicine, Lysosomal storage disease, Biomarker discovery, skin and connective tissue diseases, Child, lcsh:QH301-705.5, Spectroscopy, mucopolysaccharidosis type VI, mass spectrometry, 0303 health sciences, Mucopolysaccharidosis VI, Chemistry, General Medicine, Middle Aged, metabolomics, Computer Science Applications, Phenotype, Child, Preschool, Metabolome, Female, Metabolic Networks and Pathways, Adult, congenital, hereditary, and neonatal diseases and abnormalities, Adolescent, In silico, Computational biology, Catalysis, Article, inherited metabolic diseases, Inorganic Chemistry, 03 medical and health sciences, Young Adult, Metabolomics, medicine, Humans, Physical and Theoretical Chemistry, lysosomal storage diseases, Molecular Biology, 030304 developmental biology, Aged, Maroteaux-Lamy syndrome, Maroteaux–Lamy syndrome, Organic Chemistry, nutritional and metabolic diseases, Computational Biology, Molecular Sequence Annotation, medicine.disease, lcsh:Biology (General), lcsh:QD1-999, 030217 neurology & neurosurgery
Abstract

Metabolic phenotyping is poised as a powerful and promising tool for biomarker discovery in inherited metabolic diseases. However, few studies applied this approach to mcopolysaccharidoses (MPS). Thus, this innovative functional approach may unveil comprehensive impairments in MPS biology. This study explores mcopolysaccharidosis VI (MPS VI) or Maroteaux&ndash, Lamy syndrome (OMIM #253200) which is an autosomal recessive lysosomal storage disease caused by the deficiency of arylsulfatase B enzyme. Urine samples were collected from 16 MPS VI patients and 66 healthy control individuals. Untargeted metabolomics analysis was applied using ultra-high-performance liquid chromatography combined with ion mobility and high-resolution mass spectrometry. Furthermore, dermatan sulfate, amino acids, carnitine, and acylcarnitine profiles were quantified using liquid chromatography coupled to tandem mass spectrometry. Univariate analysis and multivariate data modeling were used for integrative analysis and discriminant metabolites selection. Pathway analysis was done to unveil impaired metabolism. The study revealed significant differential biochemical patterns using multivariate data modeling. Pathway analysis revealed that several major amino acid pathways were dysregulated in MPS VI. Integrative analysis of targeted and untargeted metabolomics data with in silico results yielded arginine-proline, histidine, and glutathione metabolism being the most affected. This study is one of the first metabolic phenotyping studies of MPS VI. The findings might shed light on molecular understanding of MPS pathophysiology to develop further MPS studies to enhance diagnosis and treatments of this rare condition.

Published
2018

5. Urinary metabolic phenotyping of mucopolysaccharidosis type I combining untargeted and targeted strategies with data modeling

Author

Farid Zerimech, Anaïs Brassier, Bruno J. Gonzalez, Stéphane Marret, Jérôme Ausseil, Carlos Afonso, Abdellah Tebani, Lenaig Abily-Donval, Frédéric M. Vaz, Bénédicte Héron, Soumeya Bekri, Monique Piraud, Pascale de Lonlay, Isabelle Schmitz-Afonso, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Endothélium microcirculatoire cérébral et lésions du système nerveux central au cours du développement (Néovasc), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Team 4 'NeoVasc' - INSERM U1245, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Biologie et Pathologie Est (CBPE), Hospices Civils de Lyon (HCL)-Centre National de Référence des Légionelles, CHU Amiens-Picardie, Centre Référence des Maladies Héréditaires du Métabolisme de l'Enfant et de l'Adulte [CHU Necker] (MaMEA Necker), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biochimie et Biologie Moléculaire [CHRU Lille] (Pôle de Biologie Pathologie Génétique), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratory Genetic Metabolic Disease, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biochimie générale [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre hospitalier universitaire de Rouen, Laboratory Genetic Metabolic Diseases, Amsterdam Gastroenterology Endocrinology Metabolism, Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Amsterdam [Amsterdam] (UvA)-Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Male, 0301 basic medicine, Adolescent, Proline, Mucopolysaccharidosis I, In silico, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Dermatan Sulfate, Arginine, Tandem mass spectrometry, Biochemistry, Mass Spectrometry, Dermatan sulfate, 03 medical and health sciences, chemistry.chemical_compound, Mucopolysaccharidosis type I, Metabolomics, Metabolome, Humans, Amino Acids, Child, Chromatography, High Pressure Liquid, Aged, chemistry.chemical_classification, Biochemistry (medical), Infant, General Medicine, Middle Aged, Glutathione, Amino acid, Phenotype, 030104 developmental biology, chemistry, Keratan Sulfate, Case-Control Studies, Child, Preschool, Multivariate Analysis, Female, Heparitin Sulfate, Algorithms
Abstract

International audience; Background =Application of metabolic phenotyping could expand the pathophysiological knowledge of mucopolysaccharidoses (MPS) and may reveal the comprehensive metabolic impairments in MPS. However, few studies applied this approach to MPS.Methods =We applied targeted and untargeted metabolic profiling in urine samples obtained from a French cohort comprising 19 MPS I and 15 MPS I treated patients along with 66 controls. For that purpose, we used ultra-high-performance liquid chromatography combined with ion mobility and high-resolution mass spectrometry following a protocol designed for large-scale metabolomics studies regarding robustness and reproducibility. Furthermore, 24 amino acids have been quantified using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Keratan sulfate, Heparan sulfate and Dermatan sulfate concentrations have also been measured using an LC-MS/MS method. Univariate and multivariate data analyses have been used to select discriminant metabolites. The mummichog algorithm has been used for pathway analysis.Results =The studied groups yielded distinct biochemical phenotypes using multivariate data analysis. Univariate statistics also revealed metabolites that differentiated the groups. Specifically, metabolites related to the amino acid metabolism. Pathway analysis revealed that several major amino acid pathways were dysregulated in MPS. Comparison of targeted and untargeted metabolomics data with in silico results yielded arginine, proline and glutathione metabolisms being the most affected.Conclusion =This study is one of the first metabolic phenotyping studies of MPS I. The findings might help to generate new hypotheses about MPS pathophysiology and to develop further targeted studies of a smaller number of potentially key metabolites.

Published
2017

6. LC-MS/MS multiplex analysis of lysosphingolipids in plasma and amniotic fluid: A novel tool for the screening of sphingolipidoses and Niemann-Pick type C disease

Author

Magali Pettazzoni, Alain Fouilhoux, Philippe Latour, Séverine Ruet, Christine Vianey-Saban, Roseline Froissart, David Cheillan, Thierry Levade, Cécile Pagan, Nathalie Guffon, Marie T. Vanier, Monique Piraud, Dominique P. Germain, Centre de Biologie et Pathologie Est (CBPE), Hospices Civils de Lyon (HCL)-Centre National de Référence des Légionelles, Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Métabolomique et maladies métaboliques, Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation Mérieux, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)

Subjects
0301 basic medicine, Male, Pathology, Embryology, Amniotic fluid, Physiology, [SDV]Life Sciences [q-bio], lcsh:Medicine, Gangliosidosis, Biochemistry, Tandem Mass Spectrometry, Prenatal Diagnosis, Medicine and Health Sciences, lcsh:Science, Chromatography, High Pressure Liquid, ComputingMilieux_MISCELLANEOUS, Multidisciplinary, Niemann-Pick Disease, Type C, Inherited Metabolic Disorders, 3. Good health, Body Fluids, Gaucher's disease, Blood, Genetic Diseases, Female, Anatomy, Cellular Structures and Organelles, Niemann–Pick disease, Research Article, Adult, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Sensitivity and Specificity, Blood Plasma, 03 medical and health sciences, Autosomal Recessive Diseases, Diagnostic Medicine, Hydrops fetalis, Sphingolipidoses, medicine, Humans, Clinical Genetics, Sphingolipids, Fetuses, business.industry, Inborn Errors of Metabolism, lcsh:R, Infant, Newborn, nutritional and metabolic diseases, Biology and Life Sciences, Cell Biology, medicine.disease, Amniotic Fluid, Sphingolipid, Fabry disease, 030104 developmental biology, Metabolic Disorders, Fabry Disease, lcsh:Q, business, Lysosomes, Biomarkers, Gaucher's Disease, Developmental Biology
Abstract

Background The biological diagnosis of sphingolipidoses currently relies on the measurement of specific enzymatic activities and/or genetic studies. Lysosphingolipids have recently emerged as potential biomarkers of sphingolipidoses and Niemann-Pick type C in plasma. Methodology We developed a sensitive and specific method enabling the simultaneous quantification of lysosphingolipids by LC-MS/MS: lysoglobotriaosylceramide for Fabry disease, lysohexosylceramide (i.e. lysoglucosylceramide and/or lysogalactosylceramide) for Gaucher and Krabbe diseases, lysosphingomyelin and its carboxylated analogue lysosphingomyelin-509 for Niemann-Pick type A or B, and C diseases, lysoGM1 ganglioside for GM1gangliosidosis and lysoGM2 ganglioside for GM2 gangliosidosis. Findings The diagnostic performances were validated in plasma samples analysing a large series of patients affected with sphingolipidoses and Niemann-Pick type C disease (n = 98), other inborn errors of metabolism (n = 23), and controls (n = 228). The multiplex measurement of lysosphingolipids allowed the screening of Fabry (including female patients and late-onset variants), Gaucher and infantile Krabbe, Niemann-Pick type A/B and C diseases with high sensitivity and specificity. LysoGM1 and LysoGM2 were elevated in most of the patients affected with GM1 and GM2 gangliosidosis respectively. In amniotic fluid supernatant from pregnancies presenting non-immune hydrops fetalis (n = 77, including previously diagnosed Gaucher (n = 5), GM1 gangliosidosis (n = 4) and galactosialidosis (n = 4) fetuses) and from normal pregnancies (n = 15), a specific and dramatic increase of lysohexosylceramide was observed only in the Gaucher amniotic fluid samples. Interpretation This multiplex assay which allows the simultaneous measurement of lysosphingolipids in plasma modifies the diagnostic strategy of sphingolipidoses and Niemann-Pick type C. Furthermore, in pregnancies presenting non-immune hydrops fetalis, lysohexosylceramide measurement in amniotic fluid offers a rapid screening of fetal Gaucher disease without waiting for glucocerebrosidase activity measurement in cultured amniocytes.

Published
2017

7. Micriamoeba tesseris nov. gen. nov. sp.: a new taxon of free-living small-sized Amoebae non-permissive to virulent Legionellae

Author

Sophie Jarraud, Patricia Doublet, Bénédicte Coupat-Goutaland, Maud Souchon, Arnaud Risler, Danièle Atlan, M. Reyrolle, Michel Pélandakis, Jérôme Briolay, Microbiologie, adaptation et pathogénie (MAP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Centre de Biologie et Pathologie Est (CBPE), Hospices Civils de Lyon (HCL)-Centre National de Référence des Légionelles, Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Immunité infection vaccination (I2V), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR128-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon

Subjects
MESH: Sequence Analysis, DNA, [SDV]Life Sciences [q-bio], Legionella pneumophila, Environmental Microbiology, Cluster Analysis, Amoeba, MESH: Phylogeny, Phylogeny, 0303 health sciences, education.field_of_study, MESH: DNA, Ribosomal, Phylogenetic tree, biology, MESH: Amoeba, MESH: Escherichia coli, MESH: Environmental Microbiology, 6. Clean water, MESH: Feeding Behavior, MESH: RNA, Protozoan, RNA, Protozoan, food.ingredient, Legionella, Population, Molecular Sequence Data, MESH: DNA, Protozoan, Microbiology, DNA, Ribosomal, Amoebozoa, Amoeba (genus), 03 medical and health sciences, food, Phylogenetics, parasitic diseases, MESH: Genes, rRNA, Escherichia coli, RNA, Ribosomal, 18S, education, 030304 developmental biology, MESH: Molecular Sequence Data, 030306 microbiology, Genes, rRNA, Feeding Behavior, Sequence Analysis, DNA, DNA, Protozoan, biology.organism_classification, MESH: Cluster Analysis, MESH: Legionella pneumophila, respiratory tract diseases, Taxon, MESH: RNA, Ribosomal, 18S
Abstract

International audience; Investigation of soil amoebae in 11 cooling towers allowed us to isolate a major unknown small-sized amoeba population (SZA). However, SZA did not appear to be specific to cooling tower ecosystems since they are also a major amoeba population found in muds isolated from different points of a water treatment plant. The SSU-rDNA sequences from SZA strains did not match any known database sequences, suggesting that SZA constitutes a new amoeba taxon. We isolated and further described one of the SZA that we named Micriamoeba tesseris. The phylogenetic analyses showed that Micriamoeba tesseris belongs to the Amebozoa and branched together with genus Echinamoeba+Vermamoeba vermiformis. Phylogenetic analyses within the Micriamoeba group distinguished different subgroups of Micriamoeba strains according to their origin, i.e. cooling tower or mud. Although Micriamoeba are able to feed on viable E. coli cells, they do not uptake virulent Legionella pneumophila strains, thus enabling them to avoid infection by Legionella. Consequently, Micriamoeba is not directly involved in L. pneumophila multiplication. However, an indirect role of Micriamoeba in Legionella risk is discussed.

Published
2012

8. Modeling neuronal defects associated with a lysosomal disorder using patient-derived induced pluripotent stem cells

Author

Diana Toli, Elise Roy, Thomas Lemonnier, Isabelle Rouvet, Delphine Bohl, Stéphane Blanchard, Stéphanie Bigou, Jean Michel Heard, Sandrine Vitry, Roseline Froissart, Rétrovirus et Transfert Génétique, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Biologie et Pathologie Est (CBPE), Hospices Civils de Lyon (HCL)-Centre National de Référence des Légionelles, Laboratoire des Maladies Héréditaires du Métabolisme, Hospices Civils de Lyon (HCL)-CHU de Lyon-GH Est-Centre de Biologie et de Pathologie Est - CBPE, Centre de Biotechnologie cellulaire, Hospices Civils de Lyon (HCL), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Biologie et de Pathologie Est - CBPE, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, MESH: Acetylglucosaminidase, [SDV]Life Sciences [q-bio], MESH: Neurons, Fibroblast growth factor, Mucopolysaccharidosis III, 0302 clinical medicine, MESH: Child, Lysosomal storage disease, Induced pluripotent stem cell, Child, MESH: Mucopolysaccharidosis III, Genetics (clinical), Cells, Cultured, Neurons, 0303 health sciences, Cell Differentiation, General Medicine, Neural stem cell, Cell biology, medicine.anatomical_structure, Child, Preschool, symbols, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Stem cell, MESH: Cells, Cultured, MESH: Cell Differentiation, MESH: Mutation, Induced Pluripotent Stem Cells, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Induced Pluripotent Stem Cells, Models, Biological, 03 medical and health sciences, symbols.namesake, Lysosome, Neurosphere, MESH: Cell Proliferation, Acetylglucosaminidase, Genetics, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, 030304 developmental biology, Cell Proliferation, MESH: Humans, MESH: Child, Preschool, MESH: Models, Biological, Golgi apparatus, Fibroblasts, medicine.disease, MESH: Male, MESH: Fibroblasts, Mutation, MESH: Heparan Sulfate Proteoglycans, Lysosomes, MESH: Female, 030217 neurology & neurosurgery, Heparan Sulfate Proteoglycans, MESH: Lysosomes
Abstract

International audience; By providing access to affected neurons, human induced pluripotent stem cells (iPSc) offer a unique opportunity to model human neurodegenerative diseases. We generated human iPSc from the skin fibroblasts of children with mucopolysaccharidosis type IIIB. In this fatal lysosomal storage disease, defective α-N-acetylglucosaminidase interrupts the degradation of heparan sulfate (HS) proteoglycans and induces cell disorders predominating in the central nervous system, causing relentless progression toward severe mental retardation. Partially digested proteoglycans, which affect fibroblast growth factor signaling, accumulated in patient cells. They impaired isolation of emerging iPSc unless exogenous supply of the missing enzyme cleared storage and restored cell proliferation. After several passages, patient iPSc starved of an exogenous enzyme continued to proliferate in the presence of fibroblast growth factor despite HS accumulation. Survival and neural differentiation of patient iPSc were comparable with unaffected controls. Whereas cell pathology was modest in floating neurosphere cultures, undifferentiated patient iPSc and their neuronal progeny expressed cell disorders consisting of storage vesicles and severe disorganization of Golgi ribbons associated with modified expression of the Golgi matrix protein GM130. Gene expression profiling in neural stem cells pointed to alterations of extracellular matrix constituents and cell-matrix interactions, whereas genes associated with lysosome or Golgi apparatus functions were downregulated. Taken together, these results suggest defective responses of patient undifferentiated stem cells and neurons to environmental cues, which possibly affect Golgi organization, cell migration and neuritogenesis. This could have potential consequences on post-natal neurological development, once HS proteoglycan accumulation becomes prominent in the affected child brain.

Published
2011

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