DOCSLIB.ORG

Scientific Report 2013 Ongoing Research 2014

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Scientific Report 2013 Ongoing Research 2014 SCIENTIFIC REPORT 2013 ONGOING RESEARCH 2014 IRCCS “Istituto Giannina Gaslini” Via Gerolamo Gaslini, 5 16147 Genova – Italy Tel. +39 010 5636 806/807 Fax +39 010 3776590 e-mail: [email protected] www.gaslini.org Some pictures of the Istituto Giannina Gaslini Nobel laureates at Gaslini: Renato Dulbecco and Rolf Zinkernagel Pope Benedict XVI visiting Gaslini Monsignor Angelo Bagnasco visiting Gaslini Some moments of the visit of the International Scientific Committee (Professors Alain Fischer, Max Cooper, Sergio Romagnani and Anthony Fauci) Annual Meeting of the SIOP Brain Tumor Sub-Committee The Germana International Centre for Studies and training (CISEF): a center of excellence which carries out educational activities in the fields of scientific research, prediatrics, organization and quality of health care services. TRIPR (Translational Research in Pediatric Rheumatology) Congress 2009 The 2 nd Training Course on Blood and Marrow Trasplantation: a course for paediatricians and pediatric nurses on HSCT in children and adolescents Despite the economic crisis afflicting our country and particularly the public health care sector, Gaslini’s scientific production remains at qualitative and quantitative levels of excellence (over 350 publications with IF). This is especially appreciable if we consider the size of Gaslini compared to other Government-funded research institutes, and if data are normalized according to the number of researchers. High quality is also attested to by the fact that Gaslini now counts among its staff 32 “Top Italian Scientists” (see table), i. e., researchers with a Hirsch index (h-index) over 30, a value considered to be of excellence (Via Academy). Advanced technology and technological innovation are essential for modern research. For this reason, thanks to co-funding from the Ministry of Health and the Regione Liguria, important investments were made in 2013 for equipment of pivotal relevance for both research and advanced diagnostics. This is essential for an institution like Gaslini, where complex diseases are diagnosed and treated. For instance, equipment for next generation sequencing (NGS) enabling the rapid diagnosis of genetic diseases was purchased, as were a cell sorter and a state-of-the-art cytofluorimeter for our Core Facilities. Furthermore, very sophisticated imaging studies are now possible thanks to the acquisition of an image streaming system and of a high-performance confocal microscope. In addition, a 3-tesla MRI scanner, an essential tool for refined diagnostics and advanced clinical research, will soon be available. Although public funding is becoming increasingly scarce, it was possible for us to award numerous two-year contracts of excellence on a competitive and strictly meritocratic basis to our most productive young researchers. Thanks to the generous and enlightened support of the Gaslini Foundation, three prizes (“Gerolamo Gaslini Awards”) were awarded to young authors of publications of particular international impact. In 2014, new calls for contracts of excellence and for prizes for the best publications were published. These actions, undertaken and implemented over the last few years, provide a definite incentive and send a clear signal that merit is held in high regard (which is certainly not a given in our country!). I want to stress my firm conviction that the application of meritocratic criteria is essential, not only for ethical reasons, but also – and mainly – to guarantee the proper functioning of any activity and to promote progress. While investing in young researchers is crucial, it is clear that actions aimed at rewarding the most deserving individuals should not be limited to prizes and contracts of excellence. Indeed, young researchers should be offered permanent positions, not only for the fair recognition of merit, but also to guarantee the continuity of research of excellence and an appropriate generational turnover. I also believe that, in a Ministry of Health-funded research institute, research should be able to rely on an appropriate number of physician-researchers who, after receiving training in a laboratory, are well acquainted with the potential of research and can speak the same language as the biologist or the biotechnologist. A well-qualified M.D. has a broader vision and a better understanding of the pathophysiological mechanisms on which he or she can base relevant experimental questions and pursue research of clinical relevance. Unfortunately, these professionals are by now very rare. Furthermore, the increasingly higher burden of clinical activities limits to a great extent the possibility to visit laboratories and to study the most recent scientific literature. In conclusion, even though today the status of research at Gaslini can be considered very positive, reduced public spending and an inadequate generational turnover are warning signs that must not be underestimated for the future of our institute. Research must be truly seen as an investment and not as a cost. Unfortunately, these words, repeated with emphasis by politicians and authorities, are rarely applied in practice. Researchers and the entire staff of Gaslini reject the idea that the institute will in the future become emblematic of a country in decline and demand that research be respected, supported, and stimulated. Research must be recognized as an important resource, a driving force of Gaslini’s progress. It would, moreover, be unacceptable to disregard what our Founder Gerolamo Gaslini declared with extraordinary acumen and foresight: “I am not a man of science, but I am perfectly aware that only by starting from scientific research, conducted under proper direction, can physicians conscientiously accomplish their difficult task”. Lorenzo Moretta ANNUAL REPORT 2013 INDEX Scientific production and results Table 1 – Publications assigned to each unit 1 Table 2 - Total publications and related IF assigned to units in 2013 2 Table 3 – Impact Factor-related data in the period 1999-2013 3 Table 4 – H-index of the Top Italian Scientists (TIS) of the Giannina Gaslini Institute 4 Scientific production year 2013 for research line Fig. 1 - Impact Factor for main research lines year 2013 5 Figure 2 – Number of Publications 6 Figure 3 - Impact Factor 6 Research lines and publications 2013 Research line 1 7 Research line 2 18 Research line 3 41 Research line 4 52 Research line 5 63 Studies and clinical trials year 2013 77 Seminars 93 Funded research projects in 2013 96 Management 100 General Direction 101 Management Control and Quality Office 102 Administrative Direction 103 Scientific Direction 104 Committees 105 Curriculum Vitae et Studiorum of Professor Lorenzo Moretta 107 Staff 110 Epidemiology, Biostatistics and Committees 112 Medical Direction 115 Pharmacy 116 Research and Diagnostics Department 119 Clinical and Experimental Immunology 120 Laboratory of Oncology 123 Laboratory of Molecular Biology 127 Laboratory of postnatal stem cells and cell therapies 129 Laboratory of Clinical Chemical Analysis 132 Immunohematology and Transfusion Medicine 136 Medical genetics 139 Centre of genetic and biochemical diagnostics of Metabolic diseases 143 Pathologic Anatomy 146 Radiology 150 Neuroradiology 154 Department of Pediatric Sciences 157 Oncology, hematology and bone marrow transplantation 158 Clinical and experimental hematology 161 Clinical oncology 164 Nephrology, dialysis and transplantation - Laboratory of physiopathology of uremia 167 Pediatric clinic 170 Clinical and Experimental Endocrinology 174 Pediatric gastroenterology with digestive endoscopy 177 Pediatric Rheumatology 180 Pediatric Pneumology and Allergology 184 Dermatology 187 Infectious diseases 189 Department of Neurosciences. Rehabilitation and Continuity of Care 192 Pediatric neurology and muscular diseases 193 Translational centre of myology and neurodegenerative diseases 198 Child neuropsychiatry 201 Physical Medicine and Rehabilitation 206 Department of Emergency and High Intensity Care 209 Pediatric Emergency and Urgency Care Medicine 210 Urgency Medicine Critical Area 213 Emergency Room and Short-Term Monitoring 216 Obstetrics and Gynecology 218 Neonatal and Pediatric Intensive Care 221 Neonatal Diseases and Intensive Care 224 Surgery Department 227 Cardiovascular surgery 228 Surgery 231 Neurosurgery 235 Orthopedics 238 Ophthalmology 240 Otolaryngology 242 Dentistry 244 Outpatient Service and Day Hospital Department (cross-functional) 245 SCIENTIFIC PRODUCTION AND RESULTS CONTRIBUTION OF UNITS TO SCIENTIFIC PRODUCTION IN 2013 Table 1 – Publications assigned to each unit (first author, last author or indermediate author) Normalized Unit N. IF IF Pediatric Neurology and Muscular Diseases 59 234.01 198.7 Laboratory of Molecular Genetics 28 141.654 127 Oncology, Hematology, and BMT 26 137.935 84.3 Pediatric Rheumatology 27 137.791 137.55 Clinical and Experimental Immunology 24 106.758 95 Lab. Physiopathology of Uremia 12 106.201 65 Nephrology, Dialysis and Transplantation 12 99.845 49.1 Laboratory of Hematology and Hemophilia 11 89.455 46 Lab. of Oncology 16 81.219 75 Cardiology 5 58.504 11 Pediatric Pneumology and Allergology 17 42.317 59 Pediatric Clinic 12 40.295 25.9 Centre of Genetic Diagnostics and Bioch. of Diseases 9 39.481 35 Laboratory of Clinical Chemical Analysis 12 38.724 51.2 Child Neuropsychiatry 11 35.254 33.6 Lab. Postnatal Stem Cells and Cell Therapies 8 33.805 31 Pediatric Gastroenterology with Endoscopy 1 29.978 7.5 Epidemiology, Biostatistics, and Committees 8 23.881 21.6
Load more

Recommended publications
  • Common Ribs of Inhibitory Synaptic Dysfunction in the Umbrella of Neurodevelopmental Disorders
    Psychology Faculty Publications Psychology 4-28-2018 Common Ribs of Inhibitory Synaptic Dysfunction in the Umbrella of Neurodevelopmental Disorders Rachel Ali Rodriguez University of Nevada, Las Vegas Christina Joya University of Nevada, Las Vegas Rochelle M. Hines University of Nevada, Las Vegas, [email protected] Follow this and additional works at: https://digitalscholarship.unlv.edu/psychology_fac_articles Part of the Neurosciences Commons Repository Citation Rodriguez, R. A., Joya, C., Hines, R. M. (2018). Common Ribs of Inhibitory Synaptic Dysfunction in the Umbrella of Neurodevelopmental Disorders. Frontiers in Molecular Neuroscience, 11 1-23. http://dx.doi.org/10.3389/fnmol.2018.00132 This Article is protected by copyright and/or related rights. It has been brought to you by Digital Scholarship@UNLV with permission from the rights-holder(s). You are free to use this Article in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s) directly, unless additional rights are indicated by a Creative Commons license in the record and/ or on the work itself. This Article has been accepted for inclusion in Psychology Faculty Publications by an authorized administrator of Digital Scholarship@UNLV. For more information, please contact [email protected]. fnmol-11-00132 April 21, 2018 Time: 12:35 # 1 REVIEW published: 24 April 2018 doi: 10.3389/fnmol.2018.00132 Common Ribs of Inhibitory Synaptic Dysfunction in the Umbrella of Neurodevelopmental Disorders Rachel Ali Rodriguez, Christina Joya and Rochelle M. Hines* Neuroscience Emphasis, Department of Psychology, University of Nevada, Las Vegas, Las Vegas, NV, United States The term neurodevelopmental disorder (NDD) is an umbrella term used to group together a heterogeneous class of disorders characterized by disruption in cognition, emotion, and behavior, early in the developmental timescale.
    [Show full text]
  • Autism Spectrum Disorders—A Genetics Review Judith H
    GENETEST REVIEW Genetics in Medicine Autism spectrum disorders—A genetics review Judith H. Miles, MD, PhD TABLE OF CONTENTS Prevalence .........................................................................................................279 Adenylosuccinate lyase deficiency ............................................................285 Clinical features................................................................................................279 Creatine deficiency syndromes..................................................................285 Core autism symptoms...................................................................................279 Smith-Lemli-Opitz syndrome.....................................................................285 Diagnostic criteria and tools..........................................................................280 Other single-gene disorders.......................................................................285 Neurologic and medical symptoms .............................................................281 Developmental syndromes of undetermined etiology..............................286 Genetics of autism...........................................................................................281 Moebius syndrome or sequence...............................................................286 Chromosomal disorders and CNVS..............................................................282 Landau-Kleffner syndrome .........................................................................286 Single-gene
    [Show full text]
  • BMC Genetics Biomed Central
    BMC Genetics BioMed Central Research article Open Access Multiple forms of atypical rearrangements generating supernumerary derivative chromosome 15 Nicholas J Wang1, Alexander S Parokonny2, Karen N Thatcher3, Jennette Driscoll2, Barbara M Malone2, Naghmeh Dorrani1, Marian Sigman4, Janine M LaSalle3 and N Carolyn Schanen*2,5,6 Address: 1Department of Human Genetics, UCLA Geffen School of Medicine, Los Angeles, California, 90095, USA, 2Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, Delaware, 19803, USA, 3Dept. of Medical Microbiology and Immunology, University of California, Davis, California, 95616, USA, 4Neuropsychiatric Institute, UCLA Geffen School of Medicine, University of California, Los Angeles, California, 90095, USA, 5Department of Biological Sciences, University of Delaware, Newark, DE, 19716, USA and 6Department of Pediatrics, Thomas Jefferson University, Philadelphia, Pennsylvania, 19107, USA Email: Nicholas J Wang - [email protected]; Alexander S Parokonny - [email protected]; Karen N Thatcher - [email protected]; Jennette Driscoll - [email protected]; Barbara M Malone - [email protected]; Naghmeh Dorrani - [email protected]; Marian Sigman - [email protected]; Janine M LaSalle - [email protected]; N Carolyn Schanen* - [email protected] * Corresponding author Published: 4 January 2008 Received: 27 August 2007 Accepted: 4 January 2008 BMC Genetics 2008, 9:2 doi:10.1186/1471-2156-9-2 This article is available from: http://www.biomedcentral.com/1471-2156/9/2 © 2008 Wang et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    [Show full text]
  • Prenatal Diagnosis of Chromosomal Disorders – Molecular Aspects
    A. Stavljenić-Rukavina Prenatal diagnosis of chromosomal disorders – molecular aspects 1. PRENATAL DIAGNOSIS OF CHROMOSOMAL DISORDERS - molecular aspects Ana Stavljenić-Rukavina Zagreb University School of Medicine, Croatia The standard measures for population health outcomes is based on maternal, infant and under five mortality rates. Health care of mother and unborn child is the most important part of population health. Therefore the care for mother and child health during pregnancy and delivery, assessment of all risks during pregnancy is of utmost importance of any health care system. It is known that perinatal mortality is caused in 20-25 percent of cases by inhaerited anomalies of fetuses and many of theese might be explained by genetic disorders. In general genetic disorder is a condition caused by abnormalities in genes or chromosomes. Chromosomes are complex bodies in cell nucleus as carriers of genes. While some diseases are due to genetic abnormalities acquired in a few cells during life, the term "genetic disease" most commonly refers to diseases present in all cells of the body and present since conception. Some genetic disorders are caused by chromosomal abnormalities due to errors in meiosis, the process which produces reproductive cells such as sperm and eggs. Examples include Down syndrome (extra chromosome 21), Turner Syndrome (45X0) and Klinefelter's syndrome (a male with 2 X chromosomes). Other genetic changes may occur during the production of germ cells by the parent. One example is the triplet expansion repeat mutations which can cause fragile X syndrome or Huntington's disease. Defective genes may also be inherited intact from the parents.
    [Show full text]
  • Copy Number Changes and Methylation
    Wang et al. Molecular Cytogenetics (2015) 8:97 DOI 10.1186/s13039-015-0198-4 RESEARCH Open Access Copy number changes and methylation patterns in an isodicentric and a ring chromosome of 15q11-q13: report of two cases and review of literature Qin Wang1, Weiqing Wu1,2, Zhiyong Xu1, Fuwei Luo1, Qinghua Zhou2,3, Peining Li2 and Jiansheng Xie1* Abstract Background: The low copy repeats (LCRs) in chromosome 15q11-q13 have been recognized as breakpoints (BP) for not only intrachromosomal deletions and duplications but also small supernumerary marker chromosomes 15, sSMC(15)s, in the forms of isodicentric chromosome or small ring chromosome. Further characterization of copy number changes and methylation patterns in these sSMC(15)s could lead to better understanding of their phenotypic consequences. Methods: Routine G-band karyotyping, fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH) analysis and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay were performed on two Chinese patients with a sSMC(15). Results: Patient 1 showed an isodicentric 15, idic(15)(q13), containing symmetrically two copies of a 7.7 Mb segment of the 15q11-q13 region by a BP3::BP3 fusion. Patient 2 showed a ring chromosome 15, r(15)(q13), with alternative one-copy and two-copy segments spanning a 12.3 Mb region. The defined methylation pattern indicated that the idic(15)(q13) and the r(15)(q13) were maternally derived. Conclusions: Results from these two cases and other reported cases from literature indicated that combined karyotyping, aCGH and MS-MLPA analyses are effective to define the copy number changes and methylation patterns for sSMC(15)s in a clinical setting.
    [Show full text]
  • Characterization by Array Comparative Genomic Hybridization
    Clin Genet 2004: 65: 477–482 Copyright # Blackwell Munksgaard 2004 Printed in Denmark. All rights reserved CLINICAL GENETICS doi: 10.1111/j.1399-0004.2004.00261.x Short Report Prader–Willi syndrome resulting from an unbalanced translocation: characterization by array comparative genomic hybridization Klein OD, Cotter PD, Albertson DG, Pinkel D, Tidyman WE, OD Kleina, PD Cottera,b,c, Moore MW, Rauen KA. Prader–Willi syndrome resulting from an DG Albertsond,e, D Pinkeld, unbalanced translocation: characterization by array comparative WE Tidymanf, MW Moorec and genomic hybridization. KA Rauena Clin Genet 2004: 65: 477–482. # Blackwell Munksgaard, 2004 aDivision of Medical Genetics, Prader–Willi syndrome (PWS) is caused by lack of expression of Department of Pediatrics, University of paternally inherited genes on chromosome 15q11!15q13. Most cases California San Francisco, San Francisco, bDivision of Medical Genetics, Children’s result from microdeletions in proximal chromosome 15q. The remainder Hospital and Research Center, Oakland, results from maternal uniparental disomy of chromosome 15, imprinting cUS Laboratories, Inc., Irvine, center defects, and rarely from balanced or unbalanced chromosome dDepartment of Laboratory Medicine, rearrangements involving chromosome 15. We report a patient with eCancer Research Institute, and multiple congenital anomalies, including craniofacial dysmorphology, fDepartment of Anatomy, University of microcephaly, bilateral cryptorchidism, and developmental delay. California San Francisco, San Francisco, Cytogenetic analysis showed a de novo 45,XY,der(5)t(5;15)(p15.2;q13), CA, USA -15 karyotype. In effect, the proband had monosomies of 5p15.2 pter ! Key words: array CGM – chromosome 5 and 15pter!15q13. Methylation polymerase chain reaction analysis of – chromosome 15 – microarray analysis – the promoter region of the SNRPN gene showed only the maternal Prader–Willi syndrome – unbalanced allele, consistent with the PWS phenotype.
    [Show full text]
  • Dup15q Syndrome: Basic Concepts in Genetics and Diagnosis
    Dup15q Syndrome: Basic Concepts in Genetics and Diagnosis Brenda Finucane, MS, LGC Genetic Counselor Associate Director, Autism & Developmental Medicine Institute Geisinger Health System Lewisburg, Pennsylvania Duplication 15q Syndrome Syndrome: recognizable pattern of physical and behavioral characteristics • Dup15q a.k.a. inverted dup15q; isodicentric 15q; partial trisomy 15; tetrasomy 15q; interstitial dup15q; etc. • Infantile hypotonia (poor muscle tone) • Subtle facial differences • Intellectual disability • Epilepsy, particularly infantile spasms • Autism spectrum disorder in majority • Sudden unexplained death in minority • Duplication of PWACR Chromosomes 46,XX Female 46,XY Male 47,XY+21 Male Copy number variations (CNV): satellite • Deletion: missing segment of genetic material p arm • Duplication: extra segment of centromere genetic material • Benign, pathogenic, and VUS q arm (variants of unknown significance) Microdeletions / microduplications: bands cannot be detected visually; diagnosed using molecular methods (FISH, microarray) Mosaicism: Two or more different genetic patterns in the same individual 47,XX,idic(15)(q11q13) Female FISH: Fluorescence In Situ Hybridization Chromosomal Microarray DNA Chip Technology that Reveals Copy Number Variation in the Human Genome Test DNA specific region of DNA Reference DNA being studied deletion no deletion / duplication duplication Deletion of genes within the 15q11.2-13.1 region 15q11.2 -13.1 cause two well-known genetic syndromes: includes the • Prader-Willi syndrome (PWS): paternal
    [Show full text]
  • FINAL Rare Epilepsy Landscape Analysis
    Rare Epilepsy Landscape Analysis (RELA) - APPENDIX July – December 2019 Ilene Penn Miller December 1, 2019 1 Rare Epilepsy Landscape Analysis (RELA) - APPENDIX APPENDIX OVERVIEW The following APPENDIX supplements the Rare Epilepsy Landscape Analysis (RELA). It includes more detailed inputs from 43 out of 44 RELA respondents. 1 respondents participated in the survey but opted out of the Appendix. APPENDIX A. RELA ANNOUNCEMENT 2 Rare Epilepsy Landscape Analysis (RELA) - APPENDIX APPENDIX B. RARES IN THE SAME SPACE Batten Disease CDKL5 GNAO1 GRIN Batten Disease Family Association CDKL5 Alliance Italy Famiglie GNAO1 Austin's Purpose and Norwegian Speilmeyer-Vogt CDKL5 Brazil Netherlands Stichting GNAO1 NL Cure Grin Association CDKL5 India The Bow Foundation GRIN2A Support Group Batten Disease Support & Research CDKL5 Research Collaborative UK Mondo UK GRIN2B Europe Association Hope4Harper GRIN2B Foundation International Foundation for CDKL5 Research Loulou Foundation ISAN LaFora Neurodegeneration with Brain Iron NORSE Accumulation Disorders (NBIA) Mickie’s Miracles Association France-Lafora BPAN Warriors Association Paratonnerre in Paris Associazione Italiana Lafora (AILA) NBIA Disorders Association (US) NORSE Institute Chelsea’s Hope Phelan McDermid Syndrome RASopathies Ring 20 SCN8A CureSHANK CFC International Ring 20 Research & Support UK Ajude o Rafa PMSF Children’s Tumor Foundation Ring Chromosome 20 Alliance Shay Emma Hammer Research Fnd Costello Syndrome Family Network The Cute Syndrome Foundation French Costello/CFC French Wishes
    [Show full text]
  • Dels and Dups and Idics, Oh
    9/30/2013 Neurogenetic Disorders Dels and Dups and Idics, >1000 genetic conditions associated with Oh My! neurodevelopmental disorders (OMIM, 2012) – Down syndrome: described in 1866 Clinical and Genetic Aspects of the 15q11-13 Region – Cornelia de Lange syndrome: 1933 – Prader-Willi syndrome: 1956 – Williams syndrome: 1961 – Angelman syndrome: 1965 – Smith-Magenis syndrome: 1986 – Phelan-McDermid syndrome: 1998 Brenda Finucane, MS, CGC – Potocki-Lupski syndrome: 2000 Associate Director, Autism & Developmental Medicine Institute Geisinger Health System …..plus hundreds of newly-identified CNVs and mutations! Lewisburg, Pennsylvania Prader-Willi Syndrome Angelman Syndrome First described in 1956 First described in 1965 Clinical diagnosis based on Clinical diagnosis based on specific pattern of physical specific pattern of physical and behavioral findings and behavioral findings The three H’s: Key features: – Hypotonia – Characteristic facial appearance – Hypogonadism – Frequent unprovoked laughter – Hyperphagia – Wide-based unsteady gait, uplifted arms Mild intellectual disability – Severe intellectual disability 1 9/30/2013 Supernumerary Markers Prader-Willi / Angelman / Dup15q • Through 1980s, reports of unidentified extra • 1981: PWS linked to 15q11-13 deletion chromosomal material associated with • 1987: 15q11-13 chromosomal deletions intellectual disability (ID), autism reported in Angelman syndrome • Some markers benign, others associated with • 1989: PWS and AS involve differentially severe disability imprinted genes in 15q region (paternal • Advances in chromosomal staining techniques deletion in PWS, maternal deletion in AS) pointed to 15q in many cases • 1990s: Maternally inherited supernumerary • Apart from ID, not thought to have a specific markers involving inverted duplications of clinical phenotype PWS/AS region; linked to autism, ID, and subtle but recognizable clinical phenotype Duplication 15q Syndrome • 1994: IDEAS established (13 families) Inverted Duplication Exchange, • a.k.a.
    [Show full text]
  • Relationships Between UBE3A and SNORD116 Expression and Features of Autism in Chromosome 15 Imprinting Disorders Emma K
    Baker et al. Translational Psychiatry (2020) 10:362 https://doi.org/10.1038/s41398-020-01034-7 Translational Psychiatry ARTICLE Open Access Relationships between UBE3A and SNORD116 expression and features of autism in chromosome 15 imprinting disorders Emma K. Baker1,2,3, Merlin G. Butler4, Samantha N. Hartin4, Ling Ling1,MinhBui5, David Francis6, Carolyn Rogers7, Michael J. Field 7, Jennie Slee8,DinushaGamage1,DavidJ.Amor 2,9 and David E. Godler 1,2 Abstract Chromosome 15 (C15) imprinting disorders including Prader–Willi (PWS), Angelman (AS) and chromosome 15 duplication (Dup15q) syndromes are severe neurodevelopmental disorders caused by abnormal expression of genes from the 15q11–q13 region, associated with abnormal DNA methylation and/or copy number changes. This study compared changes in mRNA levels of UBE3A and SNORD116 located within the 15q11–q13 region between these disorders and their subtypes and related these to the clinical phenotypes. The study cohort included 58 participants affected with a C15 imprinting disorder (PWS = 27, AS = 21, Dup15q = 10) and 20 typically developing controls. Semi- quantitative analysis of mRNA from peripheral blood mononuclear cells (PBMCs) was performed using reverse transcription droplet digital polymerase chain reaction (PCR) for UBE3A and SNORD116 normalised to a panel of internal control genes determined using the geNorm approach. Participants completed an intellectual/developmental functioning assessment and the Autism Diagnostic Observation Schedule-2nd Edition. The Dup15q group was the only condition with significantly increased UBE3A mRNA levels when compared to the control group (p < 0.001). Both fi 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; the AS and Dup15q groups also had signi cantly elevated SNORD116 mRNA levels compared to controls (AS: p < 0.0001; Dup15q: p = 0.002).
    [Show full text]
  • Genomic Designation: New Kinds of People at the Intersection of Genetics, Medicine and Social Action
    Genomic Designation: New kinds of people at the intersection of genetics, medicine and social action Daniel Navon Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2013 © 2013 Daniel Navon All rights reserved ABSTRACT Genomic Designation: New kinds of people at the intersection of genetics, medicine and social action Daniel Navon Genetics can do more than predict, explain or help treat medical conditions – it can create new ones. The social sciences have assumed that genetics must work in and through existing categories of human difference in order to inform clinical practice or social mobilization. By contrast, I go beyond the specter of reductionism and examine the emergence of new kinds of people at the intersection of genetics research, clinical practice and social action. For over fifty years, conditions like the XXX, Edwards, Fragile X and 22q11.2 Deletion Syndromes have been discovered, delineated and diagnosed strictly according to abnormalities in the genome, even in the absence of phenotypic coherence – a practice which I call ‘genomic designation’. This dissertation uses comparative historical methods, fieldwork and citation analysis to examine the history of genomic designation, its variable impact on practice and its implications for our understanding of the biosciences, medicine and social mobilization. I argue that genomic designation represents an important and growing practice that extends and challenges existing formulations of key concepts like ‘biosociality’, geneticization and the rise of a ‘molecular gaze’ in contemporary medicine. Furthermore, I show how it offers an opportunity to develop a typology of ways in which genetics can radically reconfigure medical classification.
    [Show full text]
  • Or Idic(15) Syndrome: a Case Report
    REV CUBANA GENET COMUNIT . 2012;6(1):61-63 The inv dup (15) or idic(15) syndrome: a case report. Luis A. Méndez Rosado,I Tania Cruz Mariño,II Tania Garnier Ávila,III José Hernández Gil,IV Anduriña Barrios Martínez.V Abstract the inv dup (15) syndrome to be broader than previously This report describes a patient who presented with considered. The mother had a history of two miscarriages hypotonia and epileptic seizures. She was prenatally and one molar pregnancy, it suggests she could have been diagnosed as a supernumerary chromosome carrier. By prone to unsuccessful meiosis. The existence of genetic means of Fluorescence in Situ Hybridization (FISH) or environmental factors predisposing to chromosomal using Vysis Prader-Willi/Angelman region probes, the aberrations and its correlation with the common instability marker chromosome was double positive for D15Z1 and of this chromosomal region are issues to be further quadruple positive for SNRPN. Her karyotype was thus investigated. interpreted as 47, XX,+ idic(15)(pter→q13::q13→ pter) .ish idic (15)(D15Z1++, SNRPN++++). No sphincters Keywords: Inverted duplication 15, isodicentric, marker control and signs of kyphoscoliosis may provide additional chromosome, FISH. evidence for the spectrum of clinical manifestations in Introduction chromosome, not containing the PWS/AS critical Distinctive clinical findings of the inv dup(15) region. It may be familial or de novo and its cytogenetic or idic(15) (inverted duplication of proximal description is dic(15)(q11).dic(15)(q11). chromosome 15 or isodicentric 15 chromosome) The second type of inv dup (15) has euchromatin, syndrome are represented by early central hypotonia, it includes the PWS/AS critical region.9,10 The developmental delay, intellectual disability, epilepsy cytogenetic description is dic(15)(q12 or q13).
    [Show full text]