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5 results on '"Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-HCL Groupement Hospitalier Est-Centre de référence Maladies Rénales Rares"'

1. Pharmacokinetics of mycophenolate mofetil in children with lupus and clinical findings in favour of therapeutic drug monitoring

Author

Woillard , Jean-Baptiste, Bader-Meunier , Brigitte, Salomon , Rémi, Ranchin , Bruno, Decramer , Stéphane, Fischbach , Michel, Berard , Etienne, Guigonis , Vincent, Harambat , Jérôme, Dunand , Olivier, Tenenbaum , Julie, Marquet , Pierre, Saint-Marcoux , Franck, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de néphrologie 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), Service de Néphrologie Rhumatologie Dermatologie, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-HCL Groupement Hospitalier Est-Centre de référence Maladies Rénales Rares, Service Pédiatrie - Néphrologie, CHU Toulouse [Toulouse]-Hôpital des Enfants, CHU Toulouse [Toulouse], Service Néphrologie Pédiatrique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de Néphrologie Pédiatrique, Centre Hospitalier Universitaire de Nice (CHU Nice)-Fondation LENVAL-Hopital pour Enfants, Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Service Pédiatrie, CHU Bordeaux [Bordeaux]-Centre de référence des maladies rénales rares (SORARE), Service de Néphrologie, Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Service de Pédiatrie spécialisée, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, HCL Groupement Hospitalier Est-Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de référence Maladies Rénales Rares, Marquet, Pierre, Service Néphrologie, médecine interne et hypertension pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Pharmacologie des Immunosuppresseurs et de la Transplantation ( PIST ), Université de Limoges ( UNILIM ) -CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hôpital Femme Mère Enfant [CHU - HCL] ( HFME ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -HCL Groupement Hospitalier Est-Centre de référence Maladies Rénales Rares, CHU Toulouse [Toulouse]-Hôpital des enfants Toulouse, CHU Nice-Fondation LENVAL-Hopital pour Enfants, Centre Hospitalier Universitaire de La Réunion ( CHU La Réunion ), and Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie

Subjects
Male, Adolescent, Pharmacokinetic Dynamic Relationships, PK/PD, Bayes Theorem, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Systemic Lupus Erythematosus, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, [ SDV.SP ] Life Sciences [q-bio]/Pharmaceutical sciences, Logistic Models, Area Under Curve, Child, Preschool, Humans, Lupus Erythematosus, Systemic, Female, Pharmacokinetics, Mycophenolic acid, Drug Monitoring, Child, Immunosuppressive Agents, Retrospective Studies
Abstract

International audience; AIMS: The use of mycophenolate mofetil (MMF) in children with Systemic Lupus Erythematosus (SLE) is increasing. However, the clinical benefit of its monitoring has been scarcely studied, and little is known about its pharmacokinetics in this context. The objectives of the present study were: (i) to describe mycophenolic acid (MPA; the active moiety of MMF) pharmacokinetics; (ii) to develop a Bayesian estimator (BE) allowing the determination AUC (Area under the curve) from a limited number of blood samples; and (ii) to explore the relationships between exposure indices to MPA and the clinical status in children with SLE. METHODS: This was a retrospective study including 36 children with SLE, extracted from the expert system ISBA, for whom full- pharmacokinetic profiles of MPA were collected together with clinical data. A pharmacokinetic model and a BE were developed using an iterative two-stage Bayesian approach. ROC curve analyses and logistic regressions was used to investigate the association of exposure and active disease. RESULTS: A pharmacokinetic model and a BE were developed that allowed good AUC estimation performance (bias±SD=-0.02±0.15). ROC curve analyses showed that AUC/dose

Published
2014

2. Human C-terminal CUBN variants associate with chronic proteinuria and normal renal function

Author

Marie-Josèphe Tête, Matthias Hansen, Florie Lammens, Tobias Schäfer, Albert Bensman, Alexandra Cambier, Tobias B. Huber, Christoph J. Mache, Elisa Kuhn, Christian Brix Folsted Andersen, Corinne Isnard-Bagnis, Tarunveer S. Ahluwalia, Günter Klaus, Mathilda Bedin, Fabienne Jabot-Hanin, Julien Hogan, Laure Villoing-Gaudé, Timo Wagner, Patrick Nitschke, Carole Tournant, Marcus R. Benz, Maik Grohmann, Markus Gödel, Aude Servais, Corinne Antignac, Cécile Vigneau, Ferielle Louillet, Christine Bole-Feysot, Véronique Baudouin, Iseline Bouteau, Lars Pape, Kay Latta, Carsten Bergmann, Yong Li, Vincent Morinière, Saoussen Krid, Olivier Gribouval, Olivia Boyer, Bruno Ranchin, Anna Köttgen, Matias Simons, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropathies héréditaires et rein en développement, Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Néphrologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], School of Software (THSS), Tsinghua University [Beijing], Néphropathies héréditaires et rein en développement (UMR_S 983), CHU Necker - Enfants Malades [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital Robert Debré Paris, Hôpital Robert Debré, Service de neuropédiatrie et maladies métaboliques [CHU Robert-Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré, Service de néphrologie et pédiatrie générale [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Service de Néphrologie Rhumatologie Dermatologie, HCL Groupement Hospitalier Est-Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de référence Maladies Rénales Rares, CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'urologie, néphrologie et transplantation [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Department of Pediatric Kidney, Hannover Medical School [Hannover] (MHH)-Children's Hospital, Renal Division, University Medical Center Freiburg, Freiburg, Germany, Service de Génétique Médicale [CHU Necker], 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), CHU Necker - Enfants Malades [AP-HP], Plateforme de bioinformatique, Université Paris Descartes - Paris 5 (UPD5), IT University of Copenhagen, NNF18OC0052457, Novo Nordisk Fonden, KO 3598/5-1,KIDGEM SFB1140 246781735, Deutsche Forschungsgemeinschaft, ANR-10-IAHU-01,ANR-14-ACHN-0013, Agence Nationale de la Recherche, 01GM1515C, Federal Ministry or Education and Research, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Tsinghua University [Beijing] (THU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-HCL Groupement Hospitalier Est-Centre de référence Maladies Rénales Rares, Service d'Urologie [CHU Pitié-Salpêtrière], 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), IT University of Copenhagen (ITU), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), and ANR-14-ACHN-0013,NEPHROFLY,Utilisation de Drosophila melanogaster pour étudier les maladies génétiques du rein(2014)

Subjects
Male, 0301 basic medicine, Nephrology, medicine.medical_specialty, Anemia, Megaloblastic, [SDV]Life Sciences [q-bio], Renal function, Receptors, Cell Surface, Kidney, urologic and male genital diseases, Gastroenterology, Kidney Tubules, Proximal, 03 medical and health sciences, 0302 clinical medicine, Focal segmental glomerulosclerosis, Malabsorption Syndromes, Internal medicine, Chronic kidney disease, medicine, Genetics, Albuminuria, Humans, Alport syndrome, [SDV.GEN]Life Sciences [q-bio]/Genetics, Proteinuria, business.industry, urogenital system, Vitamin B 12 Deficiency, General Medicine, medicine.disease, Cubilin, female genital diseases and pregnancy complications, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Mutation, Female, Clinical Medicine, medicine.symptom, business, Nephrotic syndrome, Genetic diseases
Abstract

International audience; BACKGROUNDProteinuria is considered an unfavorable clinical condition that accelerates renal and cardiovascular disease. However, it is not clear whether all forms of proteinuria are damaging. Mutations in CUBN cause Imerslund-Gräsbeck syndrome (IGS), which is characterized by intestinal malabsorption of vitamin B12 and in some cases proteinuria. CUBN encodes for cubilin, an intestinal and proximal tubular uptake receptor containing 27 CUB domains for ligand binding.METHODSWe used next-generation sequencing for renal disease genes to genotype cohorts of patients with suspected hereditary renal disease and chronic proteinuria. CUBN variants were analyzed using bioinformatics, structural modeling, and epidemiological methods.RESULTSWe identified 39 patients, in whom biallelic pathogenic variants in the CUBN gene were associated with chronic isolated proteinuria and early childhood onset. Since the proteinuria in these patients had a high proportion of albuminuria, glomerular diseases such as steroid-resistant nephrotic syndrome or Alport syndrome were often the primary clinical diagnosis, motivating renal biopsies and the use of proteinuria-lowering treatments. However, renal function was normal in all cases. By contrast, we did not found any biallelic CUBN variants in proteinuric patients with reduced renal function or focal segmental glomerulosclerosis. Unlike the more N-terminal IGS mutations, 37 of the 41 proteinuria-associated CUBN variants led to modifications or truncations after the vitamin B12-binding domain. Finally, we show that 4 C-terminal CUBN variants are associated with albuminuria and slightly increased GFR in meta-analyses of large population-based cohorts.CONCLUSIONCollectively, our data suggest an important role for the C-terminal half of cubilin in renal albumin reabsorption. Albuminuria due to reduced cubilin function could be an unexpectedly common benign condition in humans that may not require any proteinuria-lowering treatment or renal biopsy.FUNDINGATIP-Avenir program, Fondation Bettencourt-Schueller (Liliane Bettencourt Chair of Developmental Biology), Agence Nationale de la Recherche (ANR) Investissements d'avenir program (ANR-10-IAHU-01) and NEPHROFLY (ANR-14-ACHN-0013, to MS), Steno Collaborative Grant 2018 (NNF18OC0052457, to TSA and MS), Heisenberg Professorship of the German Research Foundation (KO 3598/5-1, to AK), Deutsche Forschungsgemeinschaft (DFG) Collaborative Research Centre (SFB) KIDGEM 1140 (project 246781735, to CB), and Federal Ministry of Education and Research (BMB) (01GM1515C, to CB).

Published
2020

3. Quality of life in adolescents with chronic kidney disease who initiate haemodialysis treatment

Author

Annie Lahoche, Isabelle Vrillon, Julie Berbis, Françoise Broux, Gwenaelle Roussey, Sylvie Cloarec, Jérôme Harambat, Michel Tsimaratos, Olivier Dunand, Mohamed Boucekine, Rémi Salomon, Soraya Menouer, Stéphanie Clavé, Bruno Ranchin, Arnaud Garnier, Marc Fila, Pascal Auquier, Georges Deschênes, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Néphrologie Rhumatologie Dermatologie, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-HCL Groupement Hospitalier Est-Centre de référence Maladies Rénales Rares, Service de néphrologie 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), Service de Néphrologie, Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Charles Nicolle [Rouen], Centre de Référence du Sud Ouest des Maladies Rénales Rares, CHU Toulouse [Toulouse]-Hôpital des Enfants, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital de Hautepierre [Strasbourg], Service de néphrologie et pédiatrie générale [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-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 Hospitalier Régional Universitaire de Nancy (CHRU Nancy), French national research program for clinical research (PHRC), HCL Groupement Hospitalier Est-Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de référence Maladies Rénales Rares, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Rouen, Normandie Université (NU)-Normandie Université (NU), CHU Trousseau [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Adult, Male, Parents, Quality of life, Gerontology, medicine.medical_specialty, Coping (psychology), Medical staff, Multivariate analysis, Adolescent, Population, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Adolescents, lcsh:RC870-923, End stage renal disease, End-stage renal disease, 03 medical and health sciences, Leisure Activities, 0302 clinical medicine, Renal Dialysis, Internal medicine, Adaptation, Psychological, Health care, medicine, Humans, Prospective Studies, Renal Insufficiency, Chronic, Child, education, Bayesian models, Initiating haemodialysis, Coping strategies, education.field_of_study, business.industry, Middle Aged, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, 3. Good health, Nephrology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Female, France, Self Report, business, Research Article, Kidney disease
Abstract

Background To describe the quality of life of adolescents initiating haemodialysis, to determine the factors associated with quality of life, and to assess coping strategies and their impact on quality of life. Methods All adolescents initiating haemodialysis between September 2013 and July 2015 in French paediatric haemodialysis centres were included. Quality of life data were collected using the “Vécu et Santé Perçue de l’Adolescent et l’Enfant” questionnaire, and coping data were collected using the Kidcope questionnaire. Adolescent’s quality of life was compared with age- and sex-matched French control. Results Thirty-two adolescents were included. Their mean age was 13.9 ± 2.0 years. The quality of life score was lowest in leisure activities and highest in relationships with medical staff. Compared with the French control, index, energy-vitality, relationships with friends, leisure activities and physical well-being scores were significantly lower in haemodialysis population. In multivariate analyses, active coping was positively associated with quality of life and especially with energy-vitality, relationships with parents and teachers, and school performance. In contrast, avoidant and negative coping were negatively associated with energy-vitality, psychological well-being and body image for avoidant coping, and body image and relationships with medical staff for negative coping. Conclusions The quality of life of haemodialysis adolescents, and mainly the dimensions of leisure activities, physical well-being, relationships with friends and energy-vitality, were significantly altered compared to that of the French population. The impact of coping strategies on quality of life seems to be important. Given the importance of quality of life and coping strategies in adolescents with chronic disease, health care professionals should integrate these aspects into care management.

Published
2019

4. Skeletal impairment in Pierson syndrome: Is there a role for lamininβ2 in bone physiology?

Author

Edith Bonnelye, Bruno Ranchin, Irma Machuca-Gayet, Justine Bacchetta, Martin Zenker, Delphine Farlay, Camille Beaufils, Caroline Freychet, Alice Fassier, Aurélia Bertholet-Thomas, Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institute of Human Genetics, University Hospital Magdeburg, Université Grenoble Alpes - UFR Médecine - Département de Maïeutique (UGA UFRMDM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre de référence des maladies rénales rares Néphrogones [CHU-HCL, Lyon], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Néphrologie Rhumatologie Dermatologie, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-HCL Groupement Hospitalier Est-Centre de référence Maladies Rénales Rares, École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université Grenoble Alpes (UGA), HCL Groupement Hospitalier Est-Hôpital Femme Mère Enfant [CHU - HCL] (HFME), and Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de référence Maladies Rénales Rares

Subjects
0301 basic medicine, medicine.medical_specialty, Histology, Nephrotic Syndrome, Adolescent, Physiology, Endocrinology, Diabetes and Metabolism, 030232 urology & nephrology, Renal function, Scoliosis, 03 medical and health sciences, 0302 clinical medicine, Laminin, Pupil Disorders, Internal medicine, Medicine, Humans, Abnormalities, Multiple, Eye Abnormalities, Congenital nephrotic syndrome, ComputingMilieux_MISCELLANEOUS, Myasthenic Syndromes, Congenital, Kidney, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, biology, business.industry, Neuromuscular Diseases, Microcoria, medicine.disease, Tacrolimus, Transplantation, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Mutation, biology.protein, Female, business
Abstract

Introduction Pierson syndrome is caused by a mutation of LAMB2, encoding for laminin β2. Clinical phenotype is variable but usually associates congenital nephrotic syndrome (CNS) and ocular abnormalities. Neuromuscular impairment has also been described. Methods We report on a 15-year old girl, suffering from Pierson Syndrome, who developed severe bone deformations during puberty. This patient initially displayed CNS and microcoria, leading to the clinical diagnosis of Pierson syndrome. Genetic analysis revealed a truncating mutation and a splice site mutation of LAMB2. The patient received a renal transplantation (R-Tx) at the age of 3. After R-Tx, renal evolution was simple, the patient receiving low-dose corticosteroids, tacrolimus and mycophenolate mofetil. At the age of 12, bone deformations progressively appeared. At the time of bone impairment, renal function was subnormal (glomerular filtration rate using iohexol clearance 50 mL/min per 1.73 m2), and parameters of calcium/phosphate metabolism were normal (calcium 2.45 mmol/L, phosphorus 1.30 mmol/L, PTH 81 ng/L, ALP 334 U/L, 25OH-D 73 nmol/L). Radiographs showed major deformations such as scoliosis, genu varum and diffuse epiphyseal abnormalities. A high resolution scanner (HR-pQCT) was performed, demonstrating a bone of “normal low” quantity and quality; major radial and cubital deformations were observed. Stainings of laminin β2 were performed on bone and renal samples from the patient and healthy controls: as expected, laminin β2 was expressed in the control kidney but not in the patient's renal tissue, and a similar pattern was observed in bone. Conclusion This is the first case of skeletal impairment ever described in Pierson syndrome. Integrin α3β1, receptor for laminin β2, are found in podocytes and osteoblasts, and the observation of both the presence of laminin β2 staining in healthy bone and its absence in the patient's bone raises the question of a potential role of laminin β2 in bone physiology.

Published
2018

5. Familial and syndromic lupus share the same phenotype as other early-onset forms of lupus

Author

François Maurier, Behrouz Kassai, Nicole Fabien, Hélène Lefebvre, Aurélia Carbasse, Maryam Piram, Irène Lemelle, Pauline Soulas-Sprauel, Bruno Ranchin, Hugues Flodrops, Eric Hachulla, Aurélia Lanteri, Brigitte Bader-Meunier, Alexandre Belot, Ulrich Meinzer, Isabelle Rouvet, Stéphane Burtey, Yanick J. Crow, Charlotte Samaille, Héloïse Reumaux, Christophe Malcus, Olivia Weill, Tiphanie Ginhoux, Frédéric Rieux-Laucat, Caroline Galeotti, V. Despert, Anne Pagnier, Isabelle Koné-Paut, Sandrine Morell Dubois, Stéphane Decramer, Service de Pédiatrie - Néphrologie, Médecine interne, Hypertension, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service d'immunologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-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)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-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)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-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), EPICIME-CIC 1407 de Lyon, Inserm, Service de Pharmacologie Clinique, hospices civils de Lyon, Centre de Biotechnologie cellulaire, Hospices Civils de Lyon (HCL), Academic Unit of Medical Genetic, University of Manchester [Manchester], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Centre de Référence des Maladies AutoInflammatoires (CeRéMAI), Centre Hospitalier de Versailles André Mignot (CHV), Unité Néphrologie Pédiatrique [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Claude Huriez [Lille], CHU Lille, Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service de médecine interne [hôpitaux privés de Metz], Hôpitaux Privés de Metz (HPMetz), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Pédiatrie [Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Pédiatrique [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Service de Néphrologie Rhumatologie Dermatologie, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-HCL Groupement Hospitalier Est-Centre de référence Maladies Rénales Rares, Service de médecine interne [Lille], Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Department of Pathology, Hôpital Femme-Mère-Enfant, Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse]-Hôpital des Enfants, CHU Toulouse [Toulouse], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-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)-École normale supérieure - Lyon (ENS Lyon)-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), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de Versailles (CHV), Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), HCL Groupement Hospitalier Est-Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de référence Maladies Rénales Rares, and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP]

Subjects
0301 basic medicine, Male, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Autoimmunity, Disease, medicine.disease_cause, Pediatrics, Severity of Illness Index, Cohort Studies, 0302 clinical medicine, immune system diseases, Epidemiology, Lupus Erythematosus, Systemic, Monogenic lupus, Age of Onset, skin and connective tissue diseases, Child, Systemic lupus erythematosus, Incidence, Age Factors, Phenotype, 3. Good health, Child, Preschool, Cohort, Disease Progression, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.medical_specialty, Adolescent, Risk Assessment, 03 medical and health sciences, Sex Factors, Rheumatology, Internal medicine, medicine, Genetics, Humans, Genetic Predisposition to Disease, Retrospective Studies, business.industry, medicine.disease, 030104 developmental biology, Disease Presentation, Immunology, business, Anti-SSA/Ro autoantibodies, Follow-Up Studies
Abstract

Objective Studies of early-onset systemic lupus erythematosus (SLE) have identified monogenic forms of the disease. The primary objective of this study was to compare the clinical and laboratory features of the first patients included in the GENIAL/LUMUGENE cohort to those reported in previous publications. The secondary objective was to determine whether subgroups with a distinctive pattern of clinical and biological features are seen in predominantly genetic forms of SLE. Methods GENIAL/LUMUGENE is a French nationwide study of the clinical, immunological, and genetic features of juvenile-onset SLE (clinicaltrials.gov # NCT01992666 ). Clinical and laboratory data from the first 64 patients younger than 18 years who were included in the first part of the study were collected retrospectively. Predefined criteria were used to divide the patients into three subgroups: syndromic SLE ( n = 10) and familial SLE ( n = 12) – both presumed to have a strong genetic component – and other forms of early-onset SLE ( n = 42). Results The predefined criteria for identifying subgroups based on knowledge of the clinical and epidemiological features of monogenic SLE showed a significantly younger age at onset in syndromic SLE ( P Conclusions In this study, clinical and epidemiological data alone failed to identify a specific patient subgroup characterized by the same disease presentation or progression. This result may be related to the small sample size or indicate marked heterogeneity of juvenile-onset SLE. Genetic studies using new sequencing techniques in these patients might identify genetic factors responsible for marked phenotypic variability.

Published
2016

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