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18 results on '"Nathalie Roux"'

1. Characterization of Loss-Of-Function KCNJ2 Mutations in Atypical Andersen Tawil Syndrome

Author: Pauline Le Tanno, Mathilde Folacci, Jean Revilloud, Laurence Faivre, Gabriel Laurent, Lucile Pinson, Pascal Amedro, Gilles Millat, Alexandre Janin, Michel Vivaudou, Nathalie Roux-Buisson, Julien Fauré, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, QH426-470, Bioinformatics, Catecholaminergic polymorphic ventricular tachycardia, Sudden death, Ryanodine receptor 2, 03 medical and health sciences, 0302 clinical medicine, Andersen–Tawil syndrome, Genetics, Medicine, Genetics (clinical), Loss function, 030304 developmental biology, Kir2.1 channel, 0303 health sciences, Pierre Robin sequence, catecholaminergic polymorphic ventricular tachycardia, Andersen-Tawil syndrome, business.industry, KCNJ2 variants, Periodic paralysis, Brief Research Report, medicine.disease, Phenotype, 3. Good health, cardiovascular system, Molecular Medicine, business, Rare disease, functionnal characterization
Abstract: Andersen-Tawil Syndrome (ATS) is a rare disease defined by the association of cardiac arrhythmias, periodic paralysis and dysmorphic features, and is caused by KCNJ2 loss-of-function mutations. However, when extracardiac symptoms are atypical or absent, the patient can be diagnosed with Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), a rare arrhythmia at high risk of sudden death, mostly due to RYR2 mutations. The identification of KCNJ2 variants in CPVT suspicion is very rare but important because beta blockers, the cornerstone of CPVT therapy, could be less efficient. We report here the cases of two patients addressed for CPVT-like phenotypes. Genetic investigations led to the identification of p. Arg82Trp and p. Pro186Gln de novo variants in the KCNJ2 gene. Functional studies showed that both variants forms of Kir2.1 monomers act as dominant negative and drastically reduced the activity of the tetrameric channel. We characterize here a new pathogenic variant (p.Pro186Gln) of KCNJ2 gene and highlight the interest of accurate cardiologic evaluation and of attention to extracardiac signs to distinguish CPVT from atypical ATS, and guide therapeutic decisions. We also confirm that the KCNJ2 gene must be investigated during CPVT molecular analysis.
Published: 2021
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2. Second Report of Chronic Granulomatous Disease in Jordan: Clinical and Genetic Description of 31 Patients From 21 Different Families, Including Families From Lybia and Iraq

Author: Faris Ghalib Bakri, Michelle Mollin, Sylvain Beaumel, Bénédicte Vigne, Nathalie Roux-Buisson, Adel Mohammed Al-Wahadneh, Raed Mohammed Alzyoud, Wail Ahmad Hayajneh, Ammar Khaled Daoud, Mohammed Elian Abu Shukair, Mansour Fuad Karadshe, Mahmoud Mohammad Sarhan, Jamal Ahmad Wadi Al-Ramahi, Julien Fauré, John Rendu, Marie Jose Stasia, Division of Infectious Diseases, Department of Medicine, Jordan University Hospital, CGD Diagnosis and Research Centre (CDiReC), Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), Laboratoire de biochimie et génétique moléculaire, CHU Grenoble, Division of Immunology, Department of Pediatric, Queen Rani Children's Hospital, Division of Immunology, Department of Pediatrics, Division of Infectious Diseases, Department of Pediatrics, Jordan University of Science & Technology, Division of Immunology, Jo PAIR clinic, Josante Medical Center, Sarhan Oncology and Stem Cell Clinics, Adjunct Faculty, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), and Centre Hospitalier Universitaire [Grenoble] (CHU)
Subjects: Male, chronic granulomatous disease, Granulomatous Disease, Chronic, medicine.disease_cause, Consanguinity, 0302 clinical medicine, Chronic granulomatous disease, Genes, X-Linked, Superoxides, immune system diseases, hemic and lymphatic diseases, Immunology and Allergy, Medicine, Child, Original Research, Genetics, 0303 health sciences, Mutation, education.field_of_study, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], autosomal recessive, 3. Good health, Child, Preschool, Iraq, Female, Immunodeficiency disorder, Adult, lcsh:Immunologic diseases. Allergy, congenital, hereditary, and neonatal diseases and abnormalities, Adolescent, Immunology, Population, Genes, Recessive, Young Adult, 03 medical and health sciences, Humans, CYBB, Sibling, education, Gene, 030304 developmental biology, Jordan, NADPH oxidase, business.industry, Infant, NADPH Oxidases, medicine.disease, innate immunodeficiency, Genetic marker, founder mutation, business, lcsh:RC581-607, 030215 immunology
Abstract: Chronic granulomatous Disease (CGD) is a rare innate immunodeficiency disorder caused by mutations in one of the six genes (CYBA, CYBB, NCF1, NCF2, NCF4, and CYBC1/EROS) encoding the superoxide-producing nicotinamide adenine dinucleotide phosphate (NADPH)—oxidase complex in phagocytes. In the Western population, the most prevalent form of CGD (about two-thirds of all cases) is the X-linked form (X-CGD) caused by mutations in CYBB. The autosomal recessive forms (AR-CGD), due to mutations in the other genes, collectively account for the remaining one-third of CGD cases. We investigated the clinical and molecular features of 22 Jordanian, 7 Libyan, and 2 Iraqi CGD patients from 21 different families. In addition, 11 sibling patients from these families were suspected to have been died from CGD as suggested by their familial and clinical history. All patients except 9 were children of consanguineous parents. Most of the patients suffered from AR-CGD, with mutations in CYBA, NCF1, and NCF2, encoding p22phox, p47phox, and p67phox proteins, respectively. AR-CGD was the most frequent form, in Jordan probably because consanguineous marriages are common in this country. Only one patient from non-consanguineous parents suffered from an X910 CGD subtype (0 indicates no protein expression). AR670 CGD and AR220 CGD appeared to be the most frequently found sub-types but also the most severe clinical forms compared to AR470 CGD. As a geographical clustering of 11 patients from eight Jordanian families exhibited the c.1171_1175delAAGCT mutation in NCF2, segregation analysis with nine polymorphic markers overlapping NCF2 indicates that a common ancestor has arisen ~1,075 years ago.
Published: 2021
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3. Variations in the TRPV1 gene are associated to exertional heat stroke

Author: Fabien van Coppenolle, Julien Fauré, John Rendu, Amandine Chatagnon, Nathalie Roux-Buisson, Dominique Figarella-Branger, Julie Brocard, Amandine Abriat, Laurent Pelletier, Emmanuel Sagui, Isabelle Marty, Sylvie Ducreux, C Bosson, Jacques Brocard, CCSD, Accord Elsevier, CHU Grenoble, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Grenoble Alpes (UGA), Groupe d'imagerie neurofonctionnelle (GIN), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomo-Cyto-Pathologie et de NeuroPathologie [Hôpital de la Timone - APHM] (ACPNP), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Fondation Maladies Rares FONDATION_WES-20150602Institut National de la Sante et de la Recherche Medicale (Inserm) Association Francaise contre les Myopathies (AFM-Telethon), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), 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: Adult, Male, Candidate gene, Heat Stroke, In silico, [SDV]Life Sciences [q-bio], Mutation, Missense, TRPV1, TRPV Cation Channels, Physical Therapy, Sports Therapy and Rehabilitation, Biology, Bioinformatics, Sudden death, 03 medical and health sciences, Malignant hyperthermia, 0302 clinical medicine, Heat exhaustion, medicine, Humans, Missense mutation, Genetic Predisposition to Disease, Orthopedics and Sports Medicine, 030212 general & internal medicine, Stroke, Gene, Exome sequencing, Whole exome sequencing, Thermogenesis, 030229 sport sciences, medicine.disease, 3. Good health, In vitro contracture test, [SDV] Life Sciences [q-bio], HEK293 Cells, Military Personnel, France
Abstract: International audience; OBJECTIVES: Exertional Heat Stroke (EHS) is one of the top three causes of sudden death in athletes. Extrinsic and intrinsic risk factors have been identified but the genetic causes still remain unclear. Our aim was to identify genes responsible for EHS, which is a necessary step to identify patients at risk and prevent crises. DESIGN: Genetic and functional laboratory studies METHODS: Whole Exome Sequencing (WES) was performed to search for candidate genes in a cohort of 15 soldiers who had a documented EHS episode. In silico and in vitro functional studies were performed to evaluate the effect of mutations identified in the candidate gene TRPV1. RESULTS: WES led to the identification of two missense variations in the TRPV1 gene. These variations were very rare or unreported in control databases and located in critical domains of the protein. In vitro functional studies revealed that both variations induce a strong modification of the channel response to one of its natural agonist, the capsaicin. CONCLUSIONS: We evidenced mutations altering channel properties of the TRPV1 gene and demonstrated that TRPV1, which is involved in thermoregulation and nociception, is a new candidate gene for EHS. Our data provide the bases to explore genetic causes and molecular mechanisms governing the pathophysiology of EHS.
Published: 2020
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4. Construction et évaluation d’un programme d’éducation thérapeutique du patient dans le domaine de la douleur liée au cancer

Author: Nathalie Roux, Maryline Feuillet, Anne-Laure Millet, Franck Lecaer, Bénédicte Clarisse, Joelle Le Garrec, Virith Sep Hieng, Marie-Claude Ropartz, Cécile Bisson, Maud Gicquère, Rachel Bignon, Virginie Prevost, Sonia Cauchin, Aline Le Chevalier, Alexandra Leconte, Carole Van Delook, Cyril Guillaumé, Marie-Christine Grach, Constance Bechet, Claire Delorme, Sylvie Gehanne, Christine Le Gal, Natacha Heutte, Isabelle Lepleux, Bodescot, Myriam, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre d’études des transformations des activités physiques et sportives (CETAPS), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut de Recherche Interdisciplinaire Homme et Société (IRIHS), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier Aunay-Bayeux (CH Aunay-Bayeux), Réseau Régional Douleur en Basse-Normandie (RRDBN), Centre Hospitalier Robert Bisson (CH Robert Bisson), Centre Hospitalier Intercommunal Alençon-Mamers (CHICAM), Centre Hospitalier Mémorial France États-Unis de Saint-Lô (CH Saint-Lô), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Fernand-Léger d'Argentan (CH Argentan), Centre Hospitalier Jacques-Monod de Flers (CH Flers), CH Centre Hospitalier Public du Cotentin (CHPC), Centre Hospitalier Avranches-Granville (CH Avranches-Granville), Pharmacie de la Croix d'Or [Paris], Les auteurs remercient pour leur soutien financier la Fondation Apicil et l'Association ARDCOM (étape 1), la société TAKEDA (étape 2), le Comité départemental de la Ligue contre le cancer de Basse-Normandie (étape 4) et l'INCa (appel d'offres RISP15-007_FP, étape 5)., Unité de Recherche clinique [Caen], UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), and Centre Hospitalier de Bayeux
Subjects: Cancer Research, Research program, Pain assessment, media_common.quotation_subject, Éducation thérapeutique du patient, Context (language use), [SDV.CAN]Life Sciences [q-bio]/Cancer, Therapeutic patient education, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), Nursing, [SDV.CAN] Life Sciences [q-bio]/Cancer, Originality, Douleur liée au cancer, Gestion de la douleur, Radiology, Nuclear Medicine and imaging, Quality (business), National level, 030212 general & internal medicine, Cancer pain, Health policy, ComputingMilieux_MISCELLANEOUS, media_common, Hematology, General Medicine, Pain management, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Évaluation de la douleur, Psychology
Abstract: Pain, one of the most feared symptoms for patients with cancer, remains insufficiently alleviated and impairs quality of life. Therapeutic patient education (TPE) is a relevant approach to this problem while allowing patients to develop skills to better manage their pain. In the "Basse-Normandie" French region, the management of pain relies on two organized networks, thus allowing proximity and accessibility for all concerned. In this context, our team has begun a broad five-step research program that is part of a regional health policy: (1) training in TPE of 10 doctor/nurse pairs; (2) identification of educational expectations of patients and their relatives in the field of cancer pain; (3) design and optimization of a TPE program dedicated to cancer pain; (4) regional pilot study aiming to assess the feasibility, quality and transferability of the program; (5) evaluation of the TPE program by interventional comparative randomization at the national level. This article aims to present the program which originality and strengths are based on collaborative work between health stakeholders. Objectives, methodology and expected results of the research phase (stages 2, 4, 5) are notably developed. The main expected outcomes are to prove the effectiveness of the program in improving the knowledge and skills of patients in the field of pain cancer in order to promote their adherence to treatment and, consequently, to enable them to better manage it. The long-term objective is to disseminate the educational approach by modifying practices that provide a mutual benefit for caregivers and patients., La douleur est l'un des symptômes les plus redoutés par les patients atteints de cancer. Elle reste insuffisamment soulagée et retentit sur leur qualité de vie. L'éducation thérapeutique du patient (ETP) constitue une approche pertinente pour répondre à cette problématique en permettant au patient de développer des compétences pour mieux gérer sa douleur. En Basse-Normandie, la prise en charge de la douleur liée au cancer s'appuie notamment sur deux réseaux structurés permettant ainsi la proximité et l'accessibilité pour tous. Dans ce contexte, nous avons construit un large programme de recherche s'inscrivant dans une politique régionale de santé, en cinq étapes : (1) formation à l'ETP de 10 binômes médecins/infirmières ; (2) identification des attentes éducatives des patients et des proches dans le domaine de la douleur ; (3) conception et optimisation d'un programme ETP ; (4) étude pilote régionale permettant d'évaluer la faisabilité, la qualité et la transférabilité du programme ; (5) évaluation du programme d'ETP par randomisation comparative interventionnelle menée à l'échelle nationale. L'objectif de cet article est de présenter la stratégie de notre approche et plus particulièrement les objectifs, la méthodologie et les résultats attendus des phases de recherche (étapes 2, 4, 5). À l'issue des cinq étapes, notre ambition est de démontrer l'efficacité du programme éducatif pour améliorer les compétences des patients leur permettant de mieux gérer leur douleur. La finalité à long terme est de diffuser la démarche éducative avec une modification des pratiques apportant un bénéfice réciproque pour les soignants et les patients.
Published: 2018
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5. Corrigendum to '22nd International Congress of the World Muscle Society, Saint Malo, France, 3rd-7th October 2017' [Neuromuscular Disorders 27S2 (2017) S51-S270]

Author: A. Chatagnon, T. Stojkovic, Julien Fauré, Nathalie Roux-Buisson, Norma B. Romero, C Bosson, J. Durigneux, François Rivier, Soledad Monges, B. Bankole, Isabelle Marty, John Rendu, CHU Grenoble, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), [GIN] Grenoble Institut des Neurosciences (GIN), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)
Subjects: 0303 health sciences, biology, business.industry, [SDV]Life Sciences [q-bio], Physiology, SAINT, Ancient history, biology.organism_classification, 03 medical and health sciences, 0302 clinical medicine, Neurology, International congress, Pediatrics, Perinatology and Child Health, Medicine, Neurology (clinical), business, Malo, 030217 neurology & neurosurgery, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: International audience
Published: 2017
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6. Functional characterization of a Central Core Disease RyR1 mutation (p.Y4864H) associated with quantitative defect in RyR1 protein

Author: Vincent Mouly, Isabelle Marty, Julien Fauré, Renée Krivosic, Nathalie Roux-Buisson, Joël Lunardi, Arnaud Lacour, Julie Brocard, Nicole Monnier, Paul D. Allen, Anne-Sophie Wozny, Marine Cacheux, Muriel Sébastien, Kamel Mamchaoui, John Rendu, Ariane Blum, INSERM U836, équipe 4, Muscles et pathologies, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Thérapie des maladies du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de biochimie et génétique moléculaire, CHU Grenoble, Département Anesthésie-Réanimation, Hôpital Roger Salengro, CHRU de Lille, Hôpital Roger Salengro, CHRU de Lille, Lille, France, Department of Molecular Biosciences, Department of Molecular Biosciences [Oslo], Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Département de neurologie [Lille], Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Roux-Buisson, Nathalie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Service de Neurologie, Hôpital Roger Salengro
Subjects: Research Report, medicine.medical_specialty, [SDV]Life Sciences [q-bio], chemistry.chemical_element, Biology, Calcium, medicine.disease_cause, Malignant hyperthermia, Calcium imaging, Central Core Disease, Internal medicine, medicine, RYR1, Mutation, Ryanodine receptor, Calcium channel, Muscle weakness, medicine.disease, musculoskeletal system, [SDV] Life Sciences [q-bio], Endocrinology, Neurology, Biochemistry, chemistry, Neurology (clinical), medicine.symptom, tissues, calcium release
Abstract: International audience; BACKGROUND: Central Core Disease (CCD) is a congenital myopathy often resulting from a mutation in RYR1 gene. Mutations in RyR1 can increase or decrease channel activity, or induce a reduction in the amount of protein. The consequences of a single mutation are sometimes multiple and the analysis of the functional effects is complex.OBJECTIVE: The consequences of the p.Y4864H mutation identified in a CCD patient have been studied regarding both RyR1 function and amount.METHODS: The amount of RyR1 in human and mouse muscles was evaluated using qRT-PCR and quantitative Western blot, and calcium release was studied using calcium imaging on primary cultures. The results were compared between human and mouse.RESULTS: The p.Y4864H mutation induced an alteration of calcium release, and in addition was associated to a reduction in the amount of RyR1 in the patient’s muscle. This suggests two possible pathophysiological mechanisms: the alteration of calcium release could result from a modification of the channel properties of RyR1 or from a RyR1 reduction. In order to discriminate between the two hypotheses, we used the heterozygous RyR1 knockout (RyR1+/-) mouse model showing a comparable RyR1 protein reduction. No reduction in calcium release was observed in primary muscle culture from these mice, and no muscle weakness was measured.CONCLUSIONS: Because the reduction in the amount of RyR1 protein has no functional consequences in the murine model, the muscle weakness observed in the patient is most likely the result of a modification of the calcium channel function of RyR1 due to the p.Y4864H mutation.
Published: 2015
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7. The role of stress test for predicting genetic mutations and future cardiac events in asymptomatic relatives of catecholaminergic polymorphic ventricular tachycardia probands

Author: Didier Klug, Isabelle Denjoy, Antoine Leenhardt, Meiso Hayashi, Fabrice Extramiana, Miyuki Hayashi, Pascale Guicheney, Alice Maltret, Nathalie Roux-Buisson, Anne Messali, Philippe Maury, Jean-Marc Lupoglazoff, Biomarqueurs CArdioNeuroVASCulaires ( BioCANVAS ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Pediatrics Department, Nippon Medical School Hospital, Cardiology Department, Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], ANTE-INSERM U836, équipe 4, Muscles et pathologies, Laboratoire de biochimie et génétique moléculaire, CHU Grenoble-CHU Grenoble, Unité de Cardiologie Néonatale, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, Service de Cardiologie A, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Unité de Rythmologie et de Stimulation Cardiaque, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Génétique, pharmacologie et physiopathologie des maladies cardiovasculaires, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), French National government (PHRC no. AOR04070, P040411), Roux-Buisson, Nathalie, Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service Cardiologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Tachycardia, Proband, Male, Pathology, Genetic testing, 030204 cardiovascular system & hematology, Ventricular tachycardia, Electrocardiography, 0302 clinical medicine, MESH : Child, Heart Rate, MESH: Child, MESH : Female, 030212 general & internal medicine, MESH: Heart Rate, Child, medicine.diagnostic_test, MESH: Adrenergic beta-Antagonists, MESH : Adult, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Ventricular Premature Complexes, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH: Young Adult, MESH : Electrocardiography, Catecholaminergic polymorphic ventricular tachycardia, Cardiology, Female, medicine.symptom, MESH : Mutation, Cardiology and Cardiovascular Medicine, Adult, medicine.medical_specialty, MESH: Mutation, Adolescent, MESH : Male, Adrenergic beta-Antagonists, MESH : Adrenergic beta-Antagonists, MESH : Young Adult, Follow-up studies, MESH : Tachycardia, Ventricular, Asymptomatic, MESH : Syncope, Syncope, 03 medical and health sciences, Young Adult, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Physiology (medical), Internal medicine, MESH : Adolescent, medicine, Humans, MESH : Ventricular Premature Complexes, MESH: Adolescent, MESH: Humans, Stress test, business.industry, MESH : Heart Rate, MESH : Humans, MESH: Adult, MESH: Death, Sudden, Cardiac, medicine.disease, MESH: Male, MESH: Electrocardiography, MESH: Ventricular Premature Complexes, MESH : Exercise Test, Death, Sudden, Cardiac, Bigeminy, MESH: Syncope, Mutation, Exercise Test, Tachycardia, Ventricular, MESH: Tachycardia, Ventricular, business, MESH: Exercise Test, MESH: Female, MESH : Death, Sudden, Cardiac
Abstract: International audience; AIMS: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmic disorder with a highly malignant clinical course. Exercise-stress test is the first-line approach to diagnose suspected individuals. We sought to elucidate the value of exercise-stress test for predicting mutations and future cardiac events in CPVT-family relatives. METHODS AND RESULTS: The present study included 67 asymptomatic relatives (24 ± 15 years) of 17 genetically positive CPVT probands, who underwent exercise-stress test without any medication and genetic testing. Exercise-stress test, which was considered positive with the induction of ventricular tachycardia or premature ventricular contractions consisting of bigeminy or couplets, was positive in 17 relatives (25%). Genetic analysis disclosed mutations in 16 of these 17 relatives (94%) and in 16 of the 50 relatives (32%) with negative exercise-stress test; the sensitivity and specificity for a positive genotype were 50 and 97%, respectively (P< 0.001). Among 32 mutation carriers, cardiac events occurred in 7 of the 16 relatives with positive and 2 of the 16 relatives with negative exercise-stress test during the follow-up period of 9.6 ± 3.8 years, and four with positive and two with negative stress test were not on regular beta-blocker treatment at these events. In the 16 relatives with positive stress test, those on beta-blocker treatment demonstrated a trend of lower cardiac event rate (Log-rank P= 0.054). CONCLUSION: In asymptomatic relatives of CPVT probands, exercise-stress test can be used as a simple diagnostic tool. Nevertheless, because of the low sensitivity for predicting mutations and future cardiac events in those with negative stress test, genetic analysis should be performed to improve patient management.
Published: 2012
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8. Evidence for genetic heterogeneity in Carvajal syndrome

Author: Nathalie Roux-Buisson, Rajae El Malti, Patrice Bouvagnet, Jean-Raymond Caignault, Nancy Nehme, Laboratoire Cardiogénétique, Centre de Biologie et pathologie Est, ANTE-INSERM U836, équipe 4, Muscles et pathologies, Laboratoire de Biochimie et Biologie Moléculaire, CHU Grenoble-CHU Grenoble, Service de Cardiologie et Pathologie Vasculaire, Service de Santé des Armées-Hôpital d'instruction des Armées, Desgenettes, and Roux-Buisson, Nathalie
Subjects: Male, [SDV]Life Sciences [q-bio], Cardiomyopathy, Dilated cardiomyopathy, Oligodontia, 030204 cardiovascular system & hematology, medicine.disease_cause, 030207 dermatology & venereal diseases, 0302 clinical medicine, MESH: Desmoplakins, MESH: Desmosomes, Keratoderma, Palmoplantar, Genetics, Mutation, MESH: Middle Aged, biology, Left bundle branch block, MESH: Genetic Heterogeneity, Desmosomes, Middle Aged, 3. Good health, Plakoglobin, [SDV] Life Sciences [q-bio], Hypo/oligodontia, Cardiomyopathies, Human, Cardiomyopathy, Dilated, Histology, MESH: Keratoderma, Palmoplantar, Pathology and Forensic Medicine, Genetic Heterogeneity, 03 medical and health sciences, stomatognathic system, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Humans, Genetic heterogeneity, Desmoplakin, Cell Biology, medicine.disease, MESH: Male, Carvajal syndrome, MESH: Hair Diseases, Desmoplakins, MESH: Cardiomyopathies, biology.protein, gamma Catenin, Hair Diseases, MESH: gamma Catenin
Abstract: International audience; Carvajal syndrome is a rare syndrome with woolly hair, palmoplantar keratosis and dilated cardiomyopathy. The inheritance of the mutation is autosomal recessive. As a causal gene, the desmoplakin gene (DSP) has so far been identified; it encodes an essential component of desmosomes, a cell-cell structure aimed at keeping cells attached to each other in tissues in which cells are often exposed to strong shear forces. Recently, familial cases of an autosomal dominant Carvajal syndrome were documented with a new feature: hypo/oligodontia. A mutation in the DSP gene was also evidenced in these latter cases. A patient was seen for cardiogenetic consultation at the University Hospital of Lyon with cardiac failure involving first degree atrioventricular block, complete left bundle branch block, non-compaction of the apex of the left ventricle and a dilated cardiomyopathy. A coronarography disclosed a complete thrombosis of the right coronary artery. At examination, he had also woolly hair, mild palmoplantar keratosis and missing teeth (essentially molars and premolars). His family history was uninformative. His DNA was screened for mutations in the DSP and plakoglobin genes but no mutation could be found. This case suggests that Carvajal syndrome with hypo/oligodontia is a heterogeneous condition in which genes other than DSP might be involved, although we cannot rule out a mutation in this gene consisting in a deletion of a single exon or a gene rearrangement.
Published: 2012
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9. Absence of triadin, a protein of the calcium release complex, is responsible for cardiac arrhythmia with sudden death in human

Author: Alain Lacampagne, Antoine Leenhardt, Julie Brocard, Nicole Monnier, Nathalie Roux-Buisson, Marine Cacheux, Julien Fauré, V. Lucet, Pierre F. Ray, Jérémy Fauconnier, Anne Fourest-Lieuvin, Isabelle Marty, Pauline Trémeaux, Isabelle Denjoy, Joël Lunardi, Philippe Mabo, Pascale Guicheney, Philippe Durand, Florence Kyndt, Vincent Probst, Hervé Le Marec, Elodie Santoni, Roux-Buisson, Nathalie, INSERM U836, équipe 4, Muscles et pathologies, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AGeing and IMagery (AGIM), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Biochimie et Génétique Moléculaire, CHU Grenoble-Hôpital Michallon-CHU Grenoble-Hôpital Michallon, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biosciences et de Biotechnologies de Grenoble (ex-IRTSV) (BIG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de Cardiologie, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité-Centre de Référence Maladies Cardiaques Héréditaires, Service de Réanimation Pédiatrique et Médecine Néonatale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Génétique, pharmacologie et physiopathologie des maladies cardiovasculaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut du thorax, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de rythmologie pédiatrique, Château des Côtes, Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biochimie et Génétique Moléculaire, CHU Grenoble-Hôpital Michallon, AGeing and IMagery (AGIM), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Biochimie et Génétique Moléculaire, INSERM, Association Française contre les myopathies (AFM), CNRS, Fondation Daniel Ducoin, PHRC, DRC du CHU Grenoble, Société Française de Myologie (SFM), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-École Pratique des Hautes Études (EPHE), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-AGeing and IMagery (AGIM), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS)-Biochimie et Génétique Moléculaire, CHU Grenoble-Hôpital Michallon-Hôpital Michallon, Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Grenoble Alpes (UGA)-Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble, AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité-Centre de Référence Maladies Cardiaques Héréditaires, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie et maladies vasculaires, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Biochimie et Génétique Moléculaire, Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Biochimie et Génétique Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF)
Subjects: Male, Muscle Proteins, MESH: Myocytes, Cardiac, 030204 cardiovascular system & hematology, MESH: Protein Isoforms, Endoplasmic Reticulum, Ryanodine receptor 2, MESH: Mice, Knockout, Mice, 0302 clinical medicine, Mutant protein, MESH: Reverse Transcriptase Polymerase Chain Reaction, Chlorocebus aethiops, Missense mutation, Protein Isoforms, Myocytes, Cardiac, MESH: Animals, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, Genetics, Mice, Knockout, 0303 health sciences, Ryanodine receptor, Reverse Transcriptase Polymerase Chain Reaction, MESH: Genetic Predisposition to Disease, General Medicine, Articles, 3. Good health, Pedigree, MESH: COS Cells, MESH: Arrhythmias, Cardiac, MESH: Calcium, COS Cells, cardiovascular system, Female, MESH: Mutation, MESH: Rats, MESH: Pedigree, Nonsense mutation, Blotting, Western, Genes, Recessive, MESH: Carrier Proteins, Biology, Catecholaminergic polymorphic ventricular tachycardia, Sudden death, 03 medical and health sciences, MESH: Muscle Proteins, MESH: Endoplasmic Reticulum, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, MESH: Blotting, Western, Genetic Predisposition to Disease, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, MESH: Mice, MESH: Genes, Recessive, 030304 developmental biology, Family Health, MESH: Humans, Cell Membrane, Arrhythmias, Cardiac, MESH: Death, Sudden, Cardiac, medicine.disease, Molecular biology, MESH: Cercopithecus aethiops, MESH: Male, Rats, Death, Sudden, Cardiac, Triadin, Mutation, Tachycardia, Ventricular, MESH: Family Health, Calcium, MESH: Tachycardia, Ventricular, Carrier Proteins, MESH: Female, MESH: Cell Membrane
Abstract: International audience; Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease so far related to mutations in the cardiac ryanodine receptor (RYR2) or the cardiac calsequestrin (CASQ2) genes. Because mutations in RYR2 or in CASQ2 are not retrieved in all CPVT cases, we searched for mutations in the physiological protein partners of RyR2 and CSQ2 in a large cohort of CPVT patients with no detected mutation in these two genes. Based on a candidate gene approach, we focused our investigations on triadin and junctin, two proteins that link RyR2 and CSQ2. Mutations in the triadin (TRDN) and in the junctin (ASPH) genes were searched in a cohort of 97 CPVT patients. We identified three mutations in triadin which cosegregated with the disease on a recessive mode of transmission in two families, but no mutation was found in junctin. Two TRDN mutations, a 4 bp deletion and a nonsense mutation, resulted in premature stop codons; the third mutation, a p.T59R missense mutation, was further studied. Expression of the p.T59R mutant in COS-7 cells resulted in intracellular retention and degradation of the mutant protein. This was confirmed after in vivo expression of the mutant triadin in triadin knock-out mice by viral transduction. In this work, we identified TRDN as a new gene responsible for an autosomal recessive form of CPVT. The mutations identified in the two families lead to the absence of the protein, thereby demonstrating the importance of triadin for the normal function of the cardiac calcium release complex in humans.
Published: 2012
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10. Functional analysis reveals splicing mutations of the CASQ2 gene in patients with CPVT: implication for genetic counselling and clinical management

Author: Alice Goldenberg, Isabelle Denjoy, Isabelle Marty, Julien Fauré, Nathalie Roux-Buisson, Joël Lunardi, Pascale Guicheney, Gian Antonio Danieli, Laurence Faivre, John Rendu, Nadine David, Olivier Barthez, Laboratoire de biochimie et génétique moléculaire, CHU Grenoble, Equipe AGIM3, Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), INSERM U836, équipe 4, Muscles et pathologies, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Laboratoire de biochimie et génétique moléculaire, CHU Grenoble-CHU Grenoble, Service de Cardiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Génétique, pharmacologie et physiopathologie des maladies cardiovasculaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, pharmacologie et physiopathologie des maladies cardiovasculaires [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Unité de cardiopédiatrie, Normandie Université (NU)-Normandie Université (NU), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de cardiologie, Department of Biology, Universita degli Studi di Padova, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Roux-Buisson, Nathalie, Génétique, pharmacologie et physiopathologie des maladies cardiovasculaires [CHU Pitié-Salpétriêre], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Cardiologie [CHU de Dijon], Università degli Studi di Padova = University of Padua (Unipd), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Proband, Male, Genetic counseling, RNA Splicing, CPVT, Molecular Sequence Data, Genetic Counseling, 030204 cardiovascular system & hematology, Biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Catecholaminergic polymorphic ventricular tachycardia, medicine.disease_cause, Bioinformatics, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Genetics, medicine, Intronic Mutation, Calsequestrin, Humans, Family, minigene, Gene, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Mutation, Base Sequence, medicine.disease, 3. Good health, Pedigree, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, HEK293 Cells, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, RNA splicing, synonymous variations, Tachycardia, Ventricular, Female, Minigene, calsequestrin 2
Abstract: International audience; Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare and severe arrhythmogenic disorder. Although usually transmitted in a recessive form, few cases of dominant mutations have been reported. Thirteen mutations in the CASQ2 gene have been reported so far in association with CPVT. We performed molecular analysis of the CASQ2 gene in 43 probands with CPVT and identified eight mutations in five patients. Six mutations were novel: one was a single nucleotide deletion, three affected consensus splice sites, and two had unknown consequences: the c.939 + 5G>C and the synonymous c.381C>T variations. We demonstrated that these two variations affected CASQ2 splicing using a splicing minigene assay. These data increased significantly the number of CASQ2 mutations described in association with CPVT, revealed the high prevalence of splicing and truncating mutations in this gene and brought new insight regarding the dominant inheritance of the disease. Moreover, our report of the first splicing abnormalities in CASQ2 caused by intronic mutation or synonymous change underlines the absolute necessity to perform extensive molecular analysis for genetic diagnosis and counseling of CPVT.Hum Mutat 32:1-5, 2011. © 2011 Wiley-Liss, Inc.
Published: 2011
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11. Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: spectrum of mutations and clinical impact in practice

Author: Philippe Charron, Guillaume Duthoit, Etienne Delacrétaz, Robert T. Frank, Catherine Coirault, Vanessa Bessirard, Guy Fontaine, Daniele Casset-Senon, François Rouzet, Yves Lecarpentier, Véronique Fressart, Didier Klug, Françoise Hidden-Lucet, Françoise Simon, Erwan Donal, Philippe Chevalier, Nathalie Roux-Buisson, Fabrice Extramiana, Olivier Dubourg, Patrice Scanu, Dagmar I. Keller, Pierre Cosnay, Bernard Hainque, Jean-Claude Deharo, Vincent Probst, Arshid Azarine, Jean-Louis Hébert, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Institut du thorax, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Est -Lyon, Service de Cardiologie A, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Ambroise Paré [AP-HP], Service de Cardiologie, Hôpital de l'Ile, Service de Cardiologie B, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de cardiologie et de pathologie vasculaire [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Universitaire de Bâle, Laboratoire de biochimie et génétique moléculaire, CHU Grenoble, Service d'Explorations Fonctionnelles Cardio-Respiratoires, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital de Bicêtre, Département de Radiologie Cardiovasculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Médecine Nucléaire [Tours], Service de Médecine Nucléaire [Paris 18eme], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Thérapie des maladies du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from Assistance Publique--Hôpitaux de Paris [PHRC programme hospitalier de recherche clinique AOM05073] and from INSERM [GISMR 0304]., Roux-Buisson, Nathalie, Unité Fonctionnelle de Cardiogénétique et Myogénétique Moléculaire et Cellulaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Chirurgie cardiaque et thoracique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CHU Trousseau [APHP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: Male, Oncology, Pathology, MESH: Desmocollins, MESH: Plakophilins, DNA Mutational Analysis, Cardiomyopathy, Arrhythmogenic right ventricular dysplasia, 030204 cardiovascular system & hematology, medicine.disease_cause, Gene, MESH: Genotype, 0302 clinical medicine, MESH: Desmoplakins, MESH: Desmosomes, Diagnosis, MESH: DNA Mutational Analysis, 0303 health sciences, Mutation, Desmoglein 2, MESH: Middle Aged, medicine.diagnostic_test, MESH: Genetic Testing, MESH: Genetic Predisposition to Disease, Desmosome, Desmosomes, Middle Aged, Prognosis, 3. Good health, MESH: Arrhythmias, Cardiac, MESH: Young Adult, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Cardiology and Cardiovascular Medicine, Adult, medicine.medical_specialty, Genotype, Desmoglein-2, Context (language use), Sudden death, MESH: Prognosis, Young Adult, 03 medical and health sciences, Physiology (medical), Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Genetic Testing, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Arrhythmogenic Right Ventricular Dysplasia, 030304 developmental biology, Genetic testing, Desmocollins, DSC2, MESH: Humans, business.industry, Arrhythmias, Cardiac, MESH: Adult, medicine.disease, MESH: Male, Desmoplakins, gamma Catenin, business, Plakophilins, MESH: Female, MESH: Desmoglein 2
Abstract: International audience; AIMS: Five desmosomal genes have been recently implicated in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) but the clinical impact of genetics remains poorly understood. We wanted to address the potential impact of genotyping. METHODS AND RESULTS: Direct sequencing of the five genes (JUP, DSP, PKP2, DSG2, and DSC2) was performed in 135 unrelated patients with ARVD/C. We identified 41 different disease-causing mutations, including 28 novel ones, in 62 patients (46%). In addition, a genetic variant of unknown significance was identified in nine additional patients (7%). Distribution of genes was 31% (PKP2), 10% (DSG2), 4.5% (DSP), 1.5% (DSC2), and 0% (JUP). The presence of desmosomal mutations was not associated with familial context but was associated with young age, symptoms, electrical substrate, and extensive structural damage. When compared with other genes, DSG2 mutations were associated with more frequent left ventricular involvement (P = 0.006). Finally, complex genetic status with multiple mutations was identified in 4% of patients and was associated with more frequent sudden death (P = 0.047). CONCLUSION: This study supports the use of genetic testing as a new diagnostic tool in ARVC/D and also suggests a prognostic impact, as the severity of the disease appears different according to the underlying gene or the presence of multiple mutations.
Published: 2010
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12. Fragmentation and immiserising specialisation : the case of the textile and clothing sector

Author: Céline Gimet, Bernard Guilhon, Nathalie Roux, Dao, Taï, Groupe d'analyse et de théorie économique (GATE Lyon Saint-Étienne), Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université Lumière - Lyon 2 (UL2)-École normale supérieure - Lyon (ENS Lyon), Centre de recherche en développement économique et finance internationale (DEFI), Groupement de Recherche en Économie Quantitative d'Aix-Marseille (GREQAM), École Centrale de Marseille (ECM)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Groupe d'Analyse et de Théorie Economique Lyon - Saint-Etienne (GATE Lyon Saint-Étienne), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), and École des hautes études en sciences sociales (EHESS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)-École des hautes études en sciences sociales (EHESS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: immiserising specialisation, offshoring,outsourcing,fragmentation,immiserising specialisation,relative wages,textile and clothing sector, offshoring, textile and clothing sector, outsourcing, fragmentation, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, [SHS.ECO] Humanities and Social Sciences/Economics and Finance, relative wages
Abstract: Working Paper GATE 2010-03; With production activity tending rapidly towards international fragmentation, this study examines the consequences for labour countries of the forms of specialisation brought about by fragmentation processes. It further addresses the risk that fragmented sectors may become excluded from greater developments within the manufacturing industry as a whole. An empirical analysis using panel data reveals that, contrary to expectation, the textile and clothing sector in labour countries does not always reap the positive benefits of this form of international trade integration. Rather, we observe a phenomenon of immiserising specialisation, due to a drop in relative wages within this sector.
Published: 2010

13. Incidence and risk factors of arrhythmic events in catecholaminergic polymorphic ventricular tachycardia

Author: Alice Maltret, Anne Messali, Pascale Guicheney, Joël Kamblock, Joël Lunardi, Antoine Leenhardt, Fabrice Extramiana, Meiso Hayashi, Elisabeth Villain, Didier Klug, Seiji Takatsuki, Nathalie Roux Buisson, Isabelle Denjoy, Jean Marc Lupoglazoff, Miyuki Hayashi, Service de Cardiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Biomarqueurs CArdioNeuroVASCulaires (BioCANVAS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie pédiatrique [CHU 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), Laboratoire de Biochimie et Génétique Moléculaire, CHU Grenoble, Unité de Cardiologie Néonatale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Service de Cardiologie A, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Cardiologie du Taaone, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), The authors received a grant from the French national government named Programme Hospitalier de Recherche Clinique No. AOR04070, P040411., Roux-Buisson, Nathalie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 ( UPD7 ), Biomarqueurs CArdioNeuroVASCulaires ( BioCANVAS ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), and Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR14-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Male, Heart disease, Ventricular tachycardia, tachycardia, MESH: Ryanodine Receptor Calcium Release Channel, 0302 clinical medicine, MESH : Child, MESH: Child, MESH: Incidence, Child, MESH: Middle Aged, Incidence, Hazard ratio, MESH: Follow-Up Studies, MESH : Incidence, 3. Good health, ventricular, MESH: Young Adult, Child, Preschool, beta-blocker, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, MESH : Young Adult, MESH : Syncope, Syncope, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH : Adolescent, Physiology (medical), death, MESH: Polymorphism, Genetic, MESH: Calsequestrin, Humans, MESH : Middle Aged, Risk factor, Beta blocker, sudden, MESH: Adolescent, Polymorphism, Genetic, MESH: Humans, MESH : Humans, MESH: Child, Preschool, MESH : Follow-Up Studies, MESH: Adult, medicine.disease, Death, Sudden, Cardiac, MESH: Family Health, MESH: Tachycardia, Ventricular, mutation, MESH: Exercise Test, MESH: Female, clinical genetics, Tachycardia, MESH : Polymorphism, Genetic, Kaplan-Meier Estimate, MESH : Child, Preschool, 030204 cardiovascular system & hematology, Sudden cardiac death, Risk Factors, MESH: Risk Factors, MESH : Female, 030212 general & internal medicine, MESH: Kaplan-Meiers Estimate, MESH : Ryanodine Receptor Calcium Release Channel, MESH: Adrenergic beta-Antagonists, Middle Aged, MESH : Adult, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH : Calsequestrin, MESH : Risk Factors, follow-up studies, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Cardiology, Female, medicine.symptom, Adult, Adolescent, medicine.drug_class, MESH : Male, Adrenergic beta-Antagonists, MESH : Adrenergic beta-Antagonists, MESH : Tachycardia, Ventricular, MESH : Family Health, Catecholaminergic polymorphic ventricular tachycardia, Young Adult, Internal medicine, medicine, Calsequestrin, Family Health, business.industry, Ryanodine Receptor Calcium Release Channel, MESH : Kaplan-Meiers Estimate, MESH: Death, Sudden, Cardiac, MESH: Male, MESH : Exercise Test, MESH: Syncope, Exercise Test, Tachycardia, Ventricular, business, MESH : Death, Sudden, Cardiac
Abstract: Background— The pathophysiological background of catecholaminergic polymorphic ventricular tachycardia is well understood, but the clinical features of this stress-induced arrhythmic disorder, especially the incidence and risk factors of arrhythmic events, have not been fully ascertained. Methods and Results— The outcome in 101 catecholaminergic polymorphic ventricular tachycardia patients, including 50 probands, was analyzed. During a mean follow-up of 7.9 years, cardiac events defined as syncope, aborted cardiac arrest, including appropriate discharges from implantable defibrillators, or sudden cardiac death occurred in 27 patients, including 2 mutation carriers with normal exercise tests. The estimated 8-year event rate was 32% in the total population and 27% and 58% in the patients with and without β-blockers, respectively. Absence of β-blockers (hazard ratio [HR], 5.48; 95% CI, 1.80 to 16.68) and younger age at diagnosis (HR, 0.54 per decade; 95% CI, 0.33 to 0.89) were independent predictors. Fatal or near-fatal events defined as aborted cardiac arrest or sudden cardiac death occurred in 13 patients, resulting in an estimated 8-year event rate of 13%. Absence of β-blockers (HR, 5.54; 95% CI, 1.17 to 26.15) and history of aborted cardiac arrest (HR, 13.01; 95% CI, 2.48 to 68.21) were independent predictors. No difference was observed in cardiac and fatal or near-fatal event rates between probands and family members. Conclusions— Cardiac and fatal or near-fatal events were not rare in both catecholaminergic polymorphic ventricular tachycardia probands and affected family members during the long-term follow-up, even while taking β-blockers, which was associated with a lower event rate. Further studies evaluating concomitant therapies are necessary to improve outcome in these patients.
Published: 2009
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14. Nickel and vanadium contamination of benthic invertebrates following the 'Erika' wreck

Author: Christophe Pécheyran, Jean-Francois Chiffoleau, Nathalie Roux, Aurélie Dufour, Laurent Chauvaud, David Amouroux, Aurélie Barats, Laboratoire Biogéochimie des Contaminants Métalliques (LBCM), Biogéochimie et Ecotoxicologie (BE), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut des sciences analytiques et de physico-chimie pour l'environnement et les materiaux (IPREM), Université de Pau et des Pays de l'Adour (UPPA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie Analytique Bio-Inorganique et Environnement (LCABIE), Université de Pau et des Pays de l'Adour (UPPA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'océanographie de Villefranche (LOV), Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre d'économie et de finances internationales (CEFI), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre atlantique, Nantes, Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de la Mer de Villefranche (IMEV), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de la Méditerranée - Aix-Marseille 2
Subjects: 0106 biological sciences, Oyster, animal structures, Monitoring, [SDV]Life Sciences [q-bio], 010501 environmental sciences, Aquatic Science, 01 natural sciences, Scallop shell, Nickel, biology.animal, Pecten maximus, [CHIM]Chemical Sciences, 14. Life underwater, Mollusca, 0105 earth and related environmental sciences, biology, 010604 marine biology & hydrobiology, fungi, Oil spill, Vanadium, Mussel, Bivalvia, biology.organism_classification, Mytilus, Oceanography, 13. Climate action, Environmental chemistry, Scallop, [SDE]Environmental Sciences, Crassostrea
Abstract: Levels of nickel and vanadium, trace metals found in high concentration in the oil spilled from the "Erika" tanker off Brittany (France) in December 1999 (41 +/- 1 and 87 +/- 3 mg kg(-1) respectively), have been monitored over a one-year period following this accidental event in several benthic invertebrates. Ni and V in mussels (Mytilus edulis) and oysters (Crassostrea gigas) soft tissues were analysed twice a month by graphite furnace atomic absorption spectrometry and a scallop (Pecten maximus) shell daily growth bands were sampled every three bands by laser ablation and analysed by ICP-MS for these two contaminants. Survey data for mollusc tissues were compared with reference data arising from the national monitoring database. Ni concentrations in dried tissues, comparable with reference data (1.8 +/- 0.9 mug g(-1) in mussels and 1.2 +/- 0.5 mug g(-1) in oysters) do not show any additional input during the whole period. Conversely, a sharp increase in vanadium concentrations (up to 4.6 and 3.2 mug g(-1d) for mussels and oysters respectively) is observed around May 2000, i.e. 5 months after the wreck, compared with the monitoring data (1.4 +/- 0.6 mug g(-1) in mussels and 1.3 +/- 0.6 mug g(-1) in oysters). Furthermore, no Ni peak is detectable in the time profiles of scallop shell growth bands where a V peak is observed also in May 2000. This study shows that although a "mussel-watch-type" network, based on the monitoring of vanadium concentration in mollusc tissues, is able to identify contamination due to oil spills, similar information might be obtained a posteriori by analysing daily growth bands of scallop shells., Les concentrations en nickel et en vanadium, métaux traces présents en quantité importante dans le fioul échappé du pétrolier "Erika" au large de la Bretagne (France) en décembre 1999 ( et mg kg -1 respectivement) ont fait l'objet d'un suivi d'un an après le naufrage chez quelques invertébrés benthiques. Ni et V ont été analysés deux fois par mois dans les tissus mous de moules (Mytilus edulis) et d'huîtres (Crassostrea gigas) par absorption atomique à four graphite et tous les trois jours dans les stries journalières de croissance des valves d'une coquille Saint-Jacques (Pecten maximus) par ICP-MS après ablation laser. Les données obtenues pour les tissus de mollusques ont été comparées avec les valeurs de références fournies par le programme national de surveillance. Durant toute la période d'étude, on n'observe pas d'apport occasionnel en nickel, dont les concentrations dans la chair séchée sont comparables aux valeurs de référence ( g g -1 chez les moules et g g -1 chez les huîtres). En revanche, une élévation importante des concentrations en vanadium (jusqu'à 4,6 et g g -1 chez les moules et les huîtres respectivement) comparées aux donnés de la surveillance ( g g -1 chez les moules et g g -1 chez les huîtres), est observée en mai 2000, soit 5 mois après le naufrage. De la même manière, aucun pic de nickel n'a été détecté dans les profils temporels de stries journalières de coquille de pectinidé alors qu'un pic de vanadium est observable en mai 2000. Cette étude montre qu'un réseau d'observation de type "mussel-watch" basé sur la surveillance des concentrations en vanadium dans les tissus de mollusques est apte à identifier une contamination due à une marée noire, et une information du même type pourrait être obtenue a posteriori en analysant les stries journalières des valves de coquilles Saint-Jacques
Published: 2004
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15. Du mythe à l’histoire

Author: Buchsenschutz, Olivier, Buchsenschutz, Olivier, Christine Bouilloc, Nathalie Roux, Ludivine Péchoux, and Oriane Hébert
Subjects: [SHS.ARCHEO] Humanities and Social Sciences/Archaeology and Prehistory, Gaulois, ComputingMilieux_MISCELLANEOUS
Published: 2014

16. Quelques réflexions sur la Gaule et les arts à la Renaissance

Author: Auclair, Valérie, Analyse Comparée des Pouvoirs (ACP), Université Paris-Est Marne-la-Vallée (UPEM), Christine Bouilloc, Nathalie Roux, Ludivine Péchoux, Oriane Hébert, and Auclair, Valérie
Subjects: [SHS.ART] Humanities and Social Sciences/Art and art history, [SHS.ART]Humanities and Social Sciences/Art and art history, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2014

17. Du mythe à l’histoire

Author: Buchsenschutz, Olivier, Celtes et Etrusques : identités, pouvoirs, échanges, Archéologie et Philologie d'Orient et d'Occident (AOROC), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Christine Bouilloc, Nathalie Roux, Ludivine Péchoux, Oriane Hébert, and École normale supérieure - Paris (ENS Paris)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS)-Paris Sciences et Lettres (PSL)-École normale supérieure - Paris (ENS Paris)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS)-Paris Sciences et Lettres (PSL)
Subjects: [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Gaulois, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2014

18. Étude de variants du gène de la calséquestrine de type 2 (Casq2)

Author: Sarrabay, Guillaume, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Nathalie Roux-Buisson
Subjects: Tachycardie ventriculaire polymorphe catécholaminergique, Calséquestrine (CASQ2), [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Complexe de relâchement du calcium
Abstract: Mémoire de DES (Diplôme d'Etudes Spécialisées) tenant lieu de thèse d'exercice; Cardiac calsequestrin (Casq2) is the major calcium storage protein in the sarcoplasmic reticulum of cardiomyocytes. It is involved in catecholaminergic polymorphic ventricular tachycardia, a severe inherited arrythmogenic disorder. CASQ2 mutations identified from 2007 to 2013 in the Molecular Genetic Laboratory of Grenoble were gathered and splicing effects of intronic and missense mutations were evaluated with prediction softwares. Functionnal analysis of two CASQ2 mutations was performed: p.S15C, a missense mutation in the signal peptide, and c.838+88T>G, a deep intronic mutation possibly involved in splicing defect. In silico predictions did not detect any splicing effect for the missense mutations but half of the mutations identified in the laboratory were shown to affect CASQ2 splicing. Wild-type and mutant c.838+88T>G minigene in vitro analysis showed no splicing defect. Wild-type and p.S15C mutant were analyzed after cell line transfections. Immunofluorescence studies, immunoblots, and glycosylation studies showed no effect of the p.S15C mutation. Polymerization studies suggested a dimerization defect for the mutant protein, although this results needs to be confirmed. In conclusion, these results could not prove the pathogenicity of the p.S15C and c.838+88T>G mutations but allowed the validation of new tools for further functional analysis in the laboratory.; La calséquestrine de type 2 (Casq2) est la protéine majeure de chélation du calcium dans le reticulum sarcoplasmique dans le muscle cardiaque. Elle est impliquée dans une sévère pathologie rythmique héréditaire : la tachycardie ventriculaire polymorphe catécholaminergique. Les mutations de CASQ2 identifiées à Grenoble au laboratoire de Biochimie et Génétique Moléculaire de 2007 à 2013 ont été recensées et l'impact sur l'épissage des mutations introniques et faux-sens a été évalué en utilisant des logiciels de prédiction. Deux mutations de CASQ2 ont fait l'objet d'une étude fonctionnelle: c.44C>G ; p.S15C localisée dans le peptide signal, et c.838+88T>G, une mutation intronique pouvant affecter l'épissage. Les prédictions in silico n'ont pas mis en évidence d'altération de l'épissage pour les variations faux-sens testées mais il apparaît que la moitié des mutations identifiées au laboratoire ont un impact sur l'épissage. L'utilisation d'un minigène sauvage et muté en 838+88T>G a permis l'étude des transcrits in vitro et n'a montré aucun impact sur l'épissage. La mutation p.S15C a été étudiée in vitro par expression ectopique. Cette mutation ne semble pas affecter la localisation de Casq2 dans le reticulum. En revanche, l'étude de polymérisation suggérait un défaut de dimérisation de la protéine mutée, bien que ce résultat soit à confirmer. En conclusion, ces résultats n'ont pas pu prouver la pathogénicité des mutations p.S15C et 838+88T>G mais ont permis de valider de nouveaux outils pour l'étude fonctionnelle des variations qui seront identifiées au laboratoire.
Published: 2013

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