Search

Your search keyword '"Jennifer Salem"' showing total 7 results
Start Over Author "Jennifer Salem"
7 results on '"Jennifer Salem"'

1. Genetic disruption of the oncogenic HMGA2–PLAG1–IGF2 pathway causes fetal growth restriction

Author

Yves Le Bouc, Frédéric Brioude, Tony Yuen, Walid Abi Habib, James T. Bennett, Madeleine D. Harbison, Thomas Edouard, Jennifer Salem, Frédérique Tixier, Anne Lienhardt-Roussie, Salah Azzi, Irène Netchine, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [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), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], University of Washington [Seattle], CHU Limoges, Hôpital Debrousse, Hospices Civils de Lyon (HCL), Icahn School of Medicine at Mount Sinai [New York] (MSSM), HAL UPMC, Gestionnaire, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)

Subjects
0301 basic medicine, Candidate gene, medicine.disease_cause, Epigenesis, Genetic, fetal growth restriction, Genotype, Original Research Article, Growth Charts, Genetics (clinical), Genetics, Regulation of gene expression, Mutation, Fetal Growth Retardation, biology, IGF2, Gene Expression Regulation, Developmental, [SDV.BDD.EO] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Pedigree, 3. Good health, DNA-Binding Proteins, Female, Signal Transduction, HMGA2, Genetic counseling, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Models, Biological, Cell Line, Silver–Russell syndrome, 03 medical and health sciences, Insulin-Like Growth Factor II, medicine, Humans, Genetic Predisposition to Disease, Epigenetics, Genetic Association Studies, PLAG1, Whole Genome Sequencing, HMGA2 Protein, Facies, Genetic Variation, medicine.disease, Silver-Russell Syndrome, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, biology.protein
Abstract

International audience; Purpose: Fetal growth is a complex process involving maternal, placental and fetal factors. The etiology of fetal growth retardation remains unknown in many cases. The aim of this study is to identify novel human mutations and genes related to Silver–Russell syndrome (SRS), a syndromic form of fetal growth retardation, usually caused by epigenetic downregulation of the potent fetal growth factor IGF2.Methods: Whole-exome sequencing was carried out on members of an SRS familial case. The candidate gene from the familial case and two other genes were screened by targeted high-throughput sequencing in a large cohort of suspected SRS patients. Functional experiments were then used to link these genes into a regulatory pathway.Results: We report the first mutations of the PLAG1 gene in humans, as well as new mutations in HMGA2 and IGF2 in six sporadic and/or familial cases of SRS. We demonstrate that HMGA2 regulates IGF2 expression through PLAG1 and in a PLAG1-independent manner.Conclusion: Genetic defects of the HMGA2–PLAG1–IGF2 pathway can lead to fetal and postnatal growth restriction, highlighting the role of this oncogenic pathway in the fine regulation of physiological fetal/postnatal growth. This work defines new genetic causes of SRS, important for genetic counseling.

Published
2018
Full Text
View/download PDF

2. 11p15 ICR1 Partial Deletions Associated withIGF2/H19DMR Hypomethylation and Silver-Russell Syndrome

Author

Claire Personnier, Sandra Chantot-Bastaraud, Walid Abi Habib, Cristina Das Neves, Jennifer Salem, Madeleine D. Harbison, Yves Le Bouc, Irène Netchine, Frédéric Brioude, Boris Keren, and Salah Azzi

Subjects
Male, 0301 basic medicine, Gene Expression, 030105 genetics & heredity, Biology, Genomic Imprinting, 03 medical and health sciences, Insulin-Like Growth Factor II, parasitic diseases, Genetics, medicine, Humans, Genetic Predisposition to Disease, Imprinting (psychology), Allele, Enhancer, Genetic Association Studies, Genetics (clinical), Sequence Deletion, Fetus, Chromosomes, Human, Pair 11, Silver–Russell syndrome, Methylation, DNA Methylation, Fibroblasts, medicine.disease, female genital diseases and pregnancy complications, Pedigree, Silver-Russell Syndrome, Child, Preschool, Overgrowth syndrome, DNA methylation, Female, RNA, Long Noncoding
Abstract

The 11p15 region harbors the IGF2/H19 imprinted domain, implicated in fetal and postnatal growth. Silver-Russell syndrome (SRS) is characterized by fetal and postnatal growth failure, and is caused principally by hypomethylation of the 11p15 imprinting control region 1 (ICR1). However, the mechanisms leading to ICR1 hypomethylation remain unknown. Maternally inherited genetic defects affecting the ICR1 domain have been associated with ICR1 hypermethylation and Beckwith-Wiedemann syndrome (an overgrowth syndrome, the clinical and molecular mirror of SRS), and paternal deletions of IGF2 enhancers have been detected in four SRS patients. However, no paternal deletions of ICR1 have ever been associated with hypomethylation of the IGF2/H19 domain in SRS. We screened for new genetic defects within the ICR1 in a cohort of 234 SRS patients with hypomethylated IGF2/H19 domain. We report deletions close to the boundaries of ICR1 on the paternal allele in one familial and two sporadic cases of SRS with ICR1 hypomethylation. These deletions are associated with hypomethylation of the remaining CBS, and decreased IGF2 expression. These results suggest that these regions are most likely required to maintain methylation after fertilization. We estimate these anomalies to occur in about 1% of SRS cases with ICR1 hypomethylation.

Published
2016
Full Text
View/download PDF

3. Chromosome 14q32.2 Imprinted Region Disruption as an Alternative Molecular Diagnosis of Silver-Russell Syndrome

Author

Sylvie Rossignol, Walid Abi Habib, Sophie Geoffron, Salah Azzi, Béatrice Dubern, Sandra Chantot-Bastaraud, Isabelle Oliver Petit, Thuy-Ai Vu-Hong, Marie-Noelle Dufourg, Ana Pinheiro Machado Canton, Catherine Pienkowski, Jennifer Salem, Blandine Esteva, Fanny Morice Picard, Bertrand Isidor, Nicole Philip, Frédéric Brioude, Alexandra Afenjar, Julien Thevenon, David Geneviève, Mélanie Fradin, Marlène Rio, Catherine Naud-Saudreau, Irène Netchine, Maithé Tauber, Christel Chalouhi, Tiffanny Busa, Virginie Steunou, Eloise Giabicani, Solveig Heide, Agnès Linglart, Madeleine D. Harbison, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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)-CHU Pitié-Salpêtrière [AP-HP], Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidade de São Paulo Medical School (FMUSP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Montpellier, Université de Montpellier (UM), Centre hospitalier universitaire de Nantes (CHU Nantes), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Thérapie génique, Génomique et Epigénomique (U 1169), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Bretagne Sud - Lorient (UBS Lorient), Université de Bretagne Sud (UBS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Génétique Médicale [CHU Necker], Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Axe 3 : organisation structurale multiéchelle des matériaux (SPCTS-AXE3), Science des Procédés Céramiques et de Traitements de Surface (SPCTS), Université de Limoges (UNILIM)-Ecole Nationale Supérieure de Céramique Industrielle (ENSCI)-Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Ecole Nationale Supérieure de Céramique Industrielle (ENSCI)-Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre de Référence du Syndrome de Prader-Willi, Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Unité de recherche sur les maladies cardiovasculaires et métaboliques, UMR S 1166, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité Fonctionnelle de Génétique Clinique [CHU Pitié Salpétrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'ORL et de Chirurgie Cervicofaciale, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Hôpital des Enfants, CHU Toulouse [Toulouse], Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Ecole Nationale Supérieure de Céramique Industrielle (ENSCI)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Institut des Procédés Appliqués aux Matériaux (IPAM), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Ecole Nationale Supérieure de Céramique Industrielle (ENSCI)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM), Service de Génétique et d'Embryologie Médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Unité Fonctionnelle de Génétique Clinique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP]-Centre de référence 'Déficiences Intellectuelles de Causes Rares' - Paris-Groupe de Recherche Clinique 'Déficience Intellectuelle et Autisme' - Paris, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Ined Inserm joint unit Elfe, Hôpital Arnaud de Villeneuve, Département de génétique médicale, maladies rares et médecine personnalisée [CHRU de Montpellier], Groupe de Recherche Clinique : Déficience Intellectuelle et Autisme (GRC), Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'endocrinologie et diabétologie pédiatriques - Le Kremlin-Bicêtre, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and MAGIC Foundation

Subjects
0301 basic medicine, Oncology, Male, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Puberty, Precocious, Chromosome Disorders, Biochemistry, Pubarche, Endocrinology, Young adult, Child, 2. Zero hunger, MEG3, Syndrome, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Uniparental disomy, 3. Good health, Phenotype, Child, Preschool, DNA methylation, Intercellular Signaling Peptides and Proteins, Female, RNA, Long Noncoding, Chromosome Deletion, Adult, medicine.medical_specialty, Adolescent, Diagnosis, Differential, 03 medical and health sciences, Genomic Imprinting, Young Adult, Internal medicine, parasitic diseases, medicine, Humans, Retrospective Studies, Chromosomes, Human, Pair 14, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, Silver–Russell syndrome, Biochemistry (medical), Calcium-Binding Proteins, Chromosome, Membrane Proteins, DNA Methylation, Uniparental Disomy, medicine.disease, Silver-Russell Syndrome, 030104 developmental biology, business, Body mass index
Abstract

International audience; Context - Silver-Russell syndrome (SRS) (mainly secondary to 11p15 molecular disruption) and Temple syndrome (TS) (secondary to 14q32.2 molecular disruption) are imprinting disorders with phenotypic (prenatal and postnatal growth retardation, early feeding difficulties) and molecular overlap. Objective - To describe the clinical overlap between SRS and TS and extensively study the molecular aspects of TS. Patients - We retrospectively collected data on 28 patients with disruption of the 14q32.2 imprinted region, identified in our center, and performed extensive molecular analysis. Results - Seventeen (60.7%) patients showed loss of methylation of the MEG3/DLK1 intergenic differentially methylated region by epimutation. Eight (28.6%) patients had maternal uniparental disomy of chromosome 14 and three (10.7%) had a paternal deletion in 14q32.2. Most patients (72.7%) had a Netchine-Harbison SRS clinical scoring system ≥4/6, and consistent with a clinical diagnosis of SRS. The mean age at puberty onset was 7.2 years in girls and 9.6 years in boys; 37.5% had premature pubarche. The body mass index of all patients increased before pubarche and/or the onset of puberty. Multilocus analysis identified multiple methylation defects in 58.8% of patients. We identified four potentially damaging genetic variants in genes encoding proteins involved in the establishment or maintenance of DNA methylation. Conclusions - Most patients with 14q32.2 disruption fulfill the criteria for a clinical diagnosis of SRS. These clinical data suggest similar management of patients with TS and SRS, with special attention to their young age at the onset of puberty and early increase of body mass index.

Published
2018
Full Text
View/download PDF

4. Effect of Cyproheptadine on Weight and Growth Velocity in Children With Silver-Russell Syndrome

Author

Jennifer Salem, Patrick Tounian, A. Lemoine, Madeleine D. Harbison, Irene Netchine, and Béatrice Dubern

Subjects
Male, medicine.medical_specialty, Cyproheptadine, urologic and male genital diseases, Growth hormone, Growth velocity, 03 medical and health sciences, 0302 clinical medicine, Child Development, Gastrointestinal Agents, 030225 pediatrics, Orexigenic, Internal medicine, medicine, Humans, heterocyclic compounds, 030212 general & internal medicine, Growth Disorders, Retrospective Studies, Gastrointestinal agent, Anthropometry, business.industry, organic chemicals, Silver–Russell syndrome, Gastroenterology, Follow up studies, Infant, respiratory system, medicine.disease, enzymes and coenzymes (carbohydrates), Silver-Russell Syndrome, Endocrinology, Child, Preschool, Pediatrics, Perinatology and Child Health, Female, business, medicine.drug, Follow-Up Studies
Abstract

Nutritional management of children with Silver-Russell syndrome (SRS) is crucial, especially before initiating growth hormone therapy. Since cyproheptadine (CYP) has been reported to be orexigenic, we retrospectively investigated the effects of CYP on changes in weight and height in patients with SRS.Anthropometric parameters (weight [W], length or height [H], weight on expected weight for height [W/H], and body mass index) were recorded for 34 children with SRS receiving CYP. We specifically analyzed the anthropometric parameters (expressed in median) in a group of 23 patients treated with CYP at baseline (M0-CYP) and every 3 months (M3 to M12-CYP) after the initiation of CYP treatment.The 23 children with SRS treated by CYP only had weight stagnation during the months preceding the start of treatment. Anthropometric parameters, especially the weight, differed significantly between M0-CYP and all other times (M3, M6, M9, M12-CYP). After 1 year of treatment, a gain in overall length/height and weight was observed (W: +1.1 standard deviations from the mean [SDS]; H: +0.5 SDS). At M3, significant improvements in W/H (74.9% vs 79.3% [P = 0.01]) and body mass index (-3.4 vs -2.4 SDS [P = 0.001]) were also observed. Twenty-one patients (91%) improved their weight by at least +0.5 SDS, and 12 (52%) by at least +1 SDS.Our results show that CYP can be effective in patients with SRS with significant improvements in growth velocity and nutritional status before initiation of growth hormone therapy. Further prospective studies are required to confirm these results.

Published
2017

5. Complex Tissue-Specific Epigenotypes in Russell-Silver Syndrome Associated with 11p15 ICR1 Hypomethylation

Author

Marilyne Le Jule, Cécile Brachet, Cristina Das Neves, Frédéric Brioude, Claudine Heinrichs, Walid Abi Habib, Virginie Steunou, Irène Netchine, Salah Azzi, Madeleine D. Harbison, Annick Blaise, Yves Le Bouc, Nathalie Thibaud, Sylvie Rossignol, and Jennifer Salem

Subjects
Adult, Cell type, Gene Expression, Russell-Silver Syndrome, Biology, Epithelium, Genomic Imprinting, chemistry.chemical_compound, Insulin-Like Growth Factor II, Clinical heterogeneity, Leukocytes, Genetics, Humans, Tissue specific, Imprinting (psychology), Child, Genetics (clinical), Skin, Chromosomes, Human, Pair 11, Postnatal growth retardation, Infant, Newborn, Mouth Mucosa, Methylation, DNA Methylation, Fibroblasts, Molecular biology, Silver-Russell Syndrome, chemistry, Organ Specificity, Child, Preschool, DNA
Abstract

Russell-Silver Syndrome (RSS) is a prenatal and postnatal growth retardation syndrome caused mainly by 11p15 ICR1 hypomethylation. Clinical presentation is heterogeneous in RSS patients with 11p15 ICR1 hypomethylation. We previously identified a subset of RSS patients with 11p15 ICR1 and multilocus hypomethylation. Here, we examine the relationships between IGF2 expression, 11p15 ICR1 methylation, and multilocus imprinting defects in various cell types from 39 RSS patients with 11p15 ICR1 hypomethylation in leukocyte DNA. 11p15 ICR1 hypomethylation was more pronounced in leukocytes than in buccal mucosa cells. Skin fibroblast IGF2 expression was correlated with the degree of ICR1 hypomethylation. Different tissue-specific multilocus methylation defects coexisted in 38% of cases, with some loci hypomethylated and others hypermethylated within the same cell type in some cases. Our new results suggest that tissue-specific epigenotypes may lead to clinical heterogeneity in RSS.

Published
2014
Full Text
View/download PDF

6. Diagnosis and management of Silver-Russell syndrome: first international consensus statement

Author

Frédéric Brioude, I. Karen Temple, Jet Bliek, Adda Grimberg, Thomas Eggermann, Gudrun E. Moore, Agnès Linglart, Klaus Mohnike, Zeynep Tümer, Edith Said, Ana Pinheiro Machado Canton, Renuka P Dias, Oluwakemi Lokulo-Sodipe, Madeleine D. Harbison, Meropi Toumba, Gerhard Binder, Béatrice Dubern, Anita C. S. Hokken-Koelega, Jennifer Salem, Deborah J G Mackay, Susan M. O’Connell, Miriam Elbracht, Irène Netchine, Justin H Davies, David Monk, Silvia Russo, Emma Wakeling, Mohamad Maghnie, Isabelle Oliver Petit, Krystyna H. Chrzanowska, Eloise Giabicani, Philip Murray, Masayo Kagami, Alexander A. L. Jorge, Tsutomu Ogata, Karen Grønskov, Pediatrics, North West london hospitals NHS Trust, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), MAGIC Foundation, Department of Clinical Genetics, University of Amsterdam [Amsterdam] (UvA), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Clinical genetic clinic, Copenhagen University Hospital, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Service d'endocrinologie pédiatrique [CHU Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fetal Growth and Developmental Group, University College of London [London] (UCL), Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, Department of Pediatrics and Medical Genetics, St. Luke's Hospital, 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), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Human Genetics and Genomic Medicine group, Faculty of Medicine, Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], and Human Genetics

Subjects
0301 basic medicine, medicine.medical_specialty, Pediatrics, Internationality, Endocrinology, Diabetes and Metabolism, Gonadotropin-Releasing Hormone/therapeutic use, Human Growth Hormone/therapeutic use, MESH: Disease Management, law.invention, Gonadotropin-Releasing Hormone, 03 medical and health sciences, Endocrinology, Randomized controlled trial, law, Internal medicine, MESH: Gonadotropin-Releasing Hormone, medicine, MESH: Human Growth Hormone, Humans, Silver-Russell Syndrome/diagnosis, Motor skill, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, MESH: Humans, Human Growth Hormone, business.industry, Adrenarche, Disease Management, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, 3. Good health, Diabetes and Metabolism, Growth hormone treatment, Natural history, Silver-Russell Syndrome, 030104 developmental biology, MESH: Silver-Russell Syndrome, Speech delay, MESH: Internationality, Small for gestational age, medicine.symptom, business, Psychosocial
Abstract

International audience; This Consensus Statement summarizes recommendations for clinical diagnosis, investigation and management of patients with Silver-Russell syndrome (SRS), an imprinting disorder that causes prenatal and postnatal growth retardation. Considerable overlap exists between the care of individuals born small for gestational age and those with SRS. However, many specific management issues exist and evidence from controlled trials remains limited. SRS is primarily a clinical diagnosis; however, molecular testing enables confirmation of the clinical diagnosis and defines the subtype. A 'normal' result from a molecular test does not exclude the diagnosis of SRS. The management of children with SRS requires an experienced, multidisciplinary approach. Specific issues include growth failure, severe feeding difficulties, gastrointestinal problems, hypoglycaemia, body asymmetry, scoliosis, motor and speech delay and psychosocial challenges. An early emphasis on adequate nutritional status is important, with awareness that rapid postnatal weight gain might lead to subsequent increased risk of metabolic disorders. The benefits of treating patients with SRS with growth hormone include improved body composition, motor development and appetite, reduced risk of hypoglycaemia and increased height. Clinicians should be aware of possible premature adrenarche, fairly early and rapid central puberty and insulin resistance. Treatment with gonadotropin-releasing hormone analogues can delay progression of central puberty and preserve adult height potential. Long-term follow up is essential to determine the natural history and optimal management in adulthood.

Published
2017
Full Text
View/download PDF

7. A prospective study validating a clinical scoring system and demonstrating phenotypical-genotypical correlations in Silver-Russell syndrome

Author

Jennifer Salem, Eli Lieber, Salah Azzi, Sandra Chantot-Bastaraud, Madeleine D. Harbison, Nathalie Thibaud, Irène Netchine, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Epigenetics Programme, The Babraham Institute [Cambridge, UK], MAGIC Foundation, Department of Psychiatry and Biobehavioral Sciences, University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Department of Pediatrics [New York], Icahn School of Medicine at Mount Sinai [New York] (MSSM), The Babraham Institute, Service de génétique et embryologie médicales [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of California-University of California, and HAL-UPMC, Gestionnaire

Subjects
medicine.medical_specialty, phenotypic-genotypic correlation, Genotype, Birth weight, [SDV.GEN] Life Sciences [q-bio]/Genetics, Russell-Silver Syndrome, Growth, Body Mass Index, Silver Russell Spectrum, Genotype-phenotype distinction, Internal medicine, Epidemiology, parasitic diseases, Genetics, Medicine, Birth Weight, Humans, Forehead, Prospective Studies, Prospective cohort study, Genetics (clinical), 2. Zero hunger, Chromosome 7 (human), [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Russell Silver Syndrome, Clinical scoring system, Genotype-Phenotype Correlations, medicine.disease, Megalencephaly, Silver-Russell Syndrome, Phenotype, Research Design, ICR1 11p15 hypomethylation and mUPD7, Small for gestational age, business, Body mass index
Abstract

International audience; Background Multiple clinical scoring systems have been proposed for Silver-Russell syndrome (SRS). Here we aimed to test a clinical scoring system for SRS and to analyse the correlation between (epi)genotype and phenotype. Subjects and methods Sixty-nine patients were examined by two physicians. Clinical scores were generated for all patients, with a new, six-item scoring system: (1) small for gestational age, birth length and/or weight ≤−2SDS, (2) postnatal growth retardation (height ≤−2SDS), (3) relative macrocephaly at birth, (4) body asymmetry, (5) feeding difficulties and/or body mass index (BMI) ≤−2SDS in toddlers; (6) protruding forehead at the age of 1–3 years. Subjects were considered to have likely SRS if they met at least four of these six criteria. Molecular investigations were performed blind to the clinical data. Results The 69 patients were classified into two groups (Likely-SRS (n=60), Unlikely-SRS (n=9)). Forty-six Likely-SRS patients (76.7%) displayed either 11p15 ICR1 hypomethylation (n=35; 58.3%) or maternal UPD of chromosome 7 (mUPD7) (n=11; 18.3%). Eight Unlikely-SRS patients had neither ICR1 hypomethylation nor mUPD7, whereas one patient had mUPD7. The clinical score and molecular results yielded four groups that differed significantly overall and for individual scoring system factors. Further molecular screening led identifying chromosomal abnormalities in Likely-SRS-double-negative and Unlikely-SRS groups. Four Likely-SRS-double negative patients carried a DLK1/GTL2 IG-DMR hypomethylation, a mUPD16; a mUPD20 and a de novo 1q21 microdeletion. Conclusions This new scoring system is very sensitive (98%) for the detection of patients with SRS with demonstrated molecular abnormalities. Given its clinical and molecular heterogeneity, SRS could be considered as a spectrum.

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results