DOCSLIB.ORG

Understanding the Premature Aging Disease Progeria and Its Link to Normal Aging

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

The Young Who Die Old: Understanding The Premature Aging Disease Progeria and its Link to Normal Aging Susan Michaelis, Ph.D. JHMI Science Writers’ Boot Camp May 7, 2018 One common view of aging: A gradual general decline of multiple cellular systems in our bodies 1978 1975 Nicholas Nixon Brown Sisters 2006 2001 2011 2014 2017 The Premature Aging Disease Hutchinson Gilford Progeria Syndrome (HGPS, progeria) Suggests a more nuanced view: Alterations in particular pathways can change the rate of aging Early onset diseases can point to particularly vulnerable components in a system A to Z: Lamin A cleavage by the ZMPSTE24 protease farnesyl S Prelamin A C O-CH3 ZMPSTE24 Mature Lamin A ZMPSTE24 cleavage is critical for health Defective lamin A processing results in the premature aging disease HGPS Sam Berns TEDx talk 2013 “My Philosophy for a Happy Life” >29 million views Sam Sam’s Mom ZMPSTE24 S Mutant Lamin A C Lamin A -O-CH3 HGPS Wild-type Mutations either in Lamin A or ZMPSTE24 cause related progeroid diseases A • Structural scaffold for the nuclear envelope • Interact with DNA, regulates gene expression Lamin A WT S C O-CH ZMPSTE24 3 progeria S C O- CH 3 Early on- there was no connection between lamin A, ZMPSTE24, and progeria HGPS First described by Dr. Jonathan Hutchinson (1886) and Dr. Hastings Gilford (1897) Rare disease (1 in 4 million) Accelerated aging: • Thin skin • Growth failure • Loss of body fat, hair • Joint and bone defects • Blood vessel defect- early onset atherosclerosis Fatal (death ~age 13) from heart attack or stroke The key advance: HGPS maps to the LMNA gene encoding Lamin A (F. Collins and N. Levy labs, 2003) Brought disparate fields together and galvanized progress Processing of farnesylated prelamin A Permanently farnesylated prelamin A is the “culprit” that causes disease FTI S X Prelamin A * C O-CH3 ZMPSTE24 Mature Lamin A Hypothesis: farnesyl transferase inhibitor (FTI), could be re-purposed to treat progeria FTI Blocks Nuclear Defects of Progeria Lamin A S C O -CH 3 S Progerin ∆50 C O-CH3 Progerin + ∆50 Caax FTI From Bench to Bedside Clinical trials with FTI’s show improved healthspan and lifespan for progeria children Gordon et al. PNAS (2012), Gordon et al. JAMA (2018) Our current studies continue a focus on fundamental ZMPSTE24 mechanism • New insights into premature aging • New insights into normal physiological aging S C O-CH ZMPSTE24 3 S C O- CH 3 ZMPSTE24 is a Novel Protease L438F L425P L462R N265S P248L W340R Y399C L94P ZMPSTE24 Progeria ZMPSTE24 Mutations Disease mutations -> Basic Mechanism -> Personalized Medicine Our recent studies suggest potential new treatment strategies for patients with certain mutations Progeria will likely provide insights into the Atherosclerosis of Normal Aging Atherosclerosis Atherosclerosis timeline • Aging is the greatest risk factor for atherosclerosis • In progeria onset of atherosclerosis is accelerated, in the absence of known risk factors like high cholesterol levels • Progeria may reveal a specific vulnerability in vessels? Understanding this vulnerability in molecular terms, could lead to more healthy vascular aging for all of us. Research takes a village!! Michaelis Lab Eric Spear Khurts Shilgardi Tim Babatz Kaiti Wood Otto Mossberg Collaborators Christine Hrycyna, Purdue Stephen Young, UCLA Liz Carpenter, SGC, Oxford, England Maya Schuldiner, Weizmann, Israel Dan Berkowitz, Johns Hopkins A “humanized yeast” system to study prelamin A processing ZMPSTE24 PTDH3 Y646 L647 10His 3myc LMNACT 15aa C SIM ZMPSTE24 100 mutation 80 60 40 % cleavage 20 preLA 0 WB: a-myc mLA ZMPSTE24 WB: a-HA 1 2 3 4 5 6 7 8 9 10 11 12 Catalytic and MAD-B Disease Mutants (blue are unstable) Blocking degradation of P248L restores prelamin A cleavage Doa10 is a yeast ubiquitin E3 ligase involved in ERAD ZMPSTE24 WT L94P P248L DOA10 + ∆ + ∆ + ∆ preLA mature LA WB: a-myc ZMPSTE24 WB: a-HA Sparing ZMPSTE24 degradation may have therapeutic value for some, but not all MAD-B patients.
Recommended publications
  • De Barsy Syndrome: Orthopedic Case Report and Literature Review

    De Barsy Syndrome: Orthopedic Case Report and Literature Review

    MOJ Orthopedics & Rheumatology De Barsy Syndrome: Orthopedic Case report and Literature Review Introduction Case Report Volume 7 Issue 5 - 2017 This condition was first described in 1968 by De Barsy who and degeneration of the elastic tissue of the cornea and skin, Jose de Jesus Guerra Jasso1*, Douglas reported a case of a patient with progeria, dwarfism, oligofrenia and since then, it is known as Barsy Syndrome or Barsy- Colmenares Bonilla2 and Loreett Ocampo Perez3 of progeroid aspect, cutis laxa, corneal opacity, intrauterine 1Pediatric Orthopedics, Hospital Regional de Alta Especialidad growthMoens-Dierckx retardation Syndrome. and severe This ismental defined retardation as the combination (although del Bajio, Mexico some will learn to speak, intelligence is less than normal) [1]. 2Pediatric Orthopedic Service, Hospital regional de alta especialidad del bajio The orthopedic manifestations are dysplasia of hip development, 3Fellow of Pediatric Orthopedics, Hospital Regional de Alta hyper laxity of severe joints, athetoid movements, scoliosis and Especialidad del Bajio, Mexico severe deformities of the foot. Epidemiology in Latin America is unknown because of its underdiagnosis and when confused *Corresponding author: Jesus Guerra Jasso, Hospital with other connective tissue pathologies (Hutchinson-Gilford Regional de Alta Especialidad del Bajio, Boulevard Milenio No. 130. Col, San Carlos la Roncha, C.P. 37660, Guanajuato, syndrome, gerodermic osteodiplasia, even Ehlers-Danlos), the Mexico, Tel: 477-267 2000; Ext-1403; life expectancy of these patients varies according to the degree of Email: penetrance and in the world literature, there are very few reports (about 50), so the diagnosis requires a challenge [2]. Received: January 13, 2017 | Published: March 21, 2017 Clinical Case and thick clamp.
  • Skeletal Phenotype of Mandibuloacral Dysplasia Associated with Mutations in ZMPSTE24

    Skeletal Phenotype of Mandibuloacral Dysplasia Associated with Mutations in ZMPSTE24

    Bone 47 (2010) 591–597 Contents lists available at ScienceDirect Bone journal homepage: www.elsevier.com/locate/bone Skeletal phenotype of mandibuloacral dysplasia associated with mutations in ZMPSTE24 Vicki J. Cunningham a,⁎, Maria Rosaria D'Apice b, Norma Licata c, Giuseppe Novelli b,d, Tim Cundy e a Child Health Centre, Northland District Health Board, New Zealand b Department of Biopathology and Diagnostic Imaging, Tor Vergata University, Rome, Italy c IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy d Ospedale San Pietro Fatebenefratelli, Rome, Italy e Department of Medicine, Faculty of Medical & Health Sciences, University of Auckland, New Zealand article info abstract Article history: Mandibuloacral dysplasia (MAD) is a rare recessively inherited premature aging disease characterized by Received 29 March 2010 skeletal and metabolic anomalies. It is part of the spectrum of diseases called laminopathies and results from Revised 3 June 2010 mutations in genes regulating the synthesis of the nuclear laminar protein, lamin A. Homozygous or Accepted 5 June 2010 compound heterozygous mutations in the LMNA gene, which encodes both the precursor protein prelamin A Available online 13 June 2010 and lamin C, are the commonest cause of MAD type A. In a few cases of MAD type B, mutations have been fi Edited by: S. Ralston identi ed in the ZMPSTE24 gene encoding a zinc metalloproteinase important in the post-translational modification of lamin A. Here we describe a new case of MAD resulting from compound heterozygote Keywords: mutations in ZMPSTE24 (p.N256S/p.Y70fs). The patient had typical skeletal changes of MAD, but in addition a Mandibuloacral dysplasia number of unusual skeletal features including neonatal tooth eruption, amorphous calcific deposits, ZMPSTE24 submetaphyseal erosions, vertebral beaking, severe cortical osteoporosis and delayed fracture healing.
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus

    A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus

    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
  • The Progeria Syndrome Fact Sheet

    The Progeria Syndrome Fact Sheet

    HUTCHINSON-GILFORD PROGERIA SYNDROME FREQUENTLY ASKED QUESTIONS WHAT IS PROGERIA? Hutchinson-Gilford Progeria Syndrome “Progeria” or “HGPS” is a rare, fatal genetic condition characterized by an appearance of accelerated aging in children. Its name is derived from the Greek and means "prematurely old." While there are different forms of Progeria*, the classic type is Hutchinson- Gilford Progeria Syndrome, which was named after the doctors who first described it in England: in 1886 by Dr. Jonathan Hutchinson, and in 1897 by Dr. Hastings Gilford. HOW COMMON IS PROGERIA? Progeria affects approximately 1 in 4 - 8 million newborns. It affects both sexes equally and all races. In the past 15 years, children with Progeria have been reported all over the world , including in: Algeria Cuba Ireland Peru Sweden Argentina Denmark Israel Philippines Switzerland Australia Dominican Italy Poland Turkey Austria Republic Japan Portugal United States Belgium Egypt Libya Puerto Rico Venezuela Brazil England Mexico Romania Vietnam Canada France Morocco South Africa Yugoslavia China Germany Netherlands South Korea Columbia India Pakistan Spain WHAT ARE THE FEATURES OF PROGERIA? Although they are born looking healthy, most children with Progeria begin to display many characteristics of Progeria within the first year of life. Progeria signs include growth failure, loss of body fat and hair, aged-looking skin, stiffness of joints, hip dislocation, generalized atherosclerosis, cardiovascular (heart) disease and stroke. The children have a remarkably similar appearance, despite differing ethnic backgrounds. Children with Progeria die of atherosclerosis (heart disease) at an average age of thirteen years (with a range of about 8 – 21 years). WHAT DOES PROGERIA HAVE TO DO WITH AGING? Children with Progeria are genetically predisposed to premature, progressive heart disease.
  • Role of Zmpste24 in Prelamin a Maturation. Douglas Paul Corrigan East Tennessee State University

    Role of Zmpste24 in Prelamin a Maturation. Douglas Paul Corrigan East Tennessee State University

    East Tennessee State University Digital Commons @ East Tennessee State University Electronic Theses and Dissertations Student Works 8-2005 Role of Zmpste24 in Prelamin A Maturation. Douglas Paul Corrigan East Tennessee State University Follow this and additional works at: https://dc.etsu.edu/etd Part of the Medical Sciences Commons Recommended Citation Corrigan, Douglas Paul, "Role of Zmpste24 in Prelamin A Maturation." (2005). Electronic Theses and Dissertations. Paper 1046. https://dc.etsu.edu/etd/1046 This Dissertation - Open Access is brought to you for free and open access by the Student Works at Digital Commons @ East Tennessee State University. It has been accepted for inclusion in Electronic Theses and Dissertations by an authorized administrator of Digital Commons @ East Tennessee State University. For more information, please contact [email protected]. Role of Zmpste24 in Prelamin A Maturation A dissertation presented to the faculty of the Department of Biochemistry and Molecular Biology East Tennessee State University In partial fulfillment of the requirements for the degree Doctor of Philosophy in Biomedical Sciences by Douglas P. Corrigan August 2005 Antonio E. Rusinol, Chair Ranjan N. Chakraborty Michael S. Sinensky Douglas P. Thewke M. Stephen Trent Keywords: Zmpste24, Prelamin A, endoproteolysis, prenylation, farnesylation ABSTRACT Role of Zmpste24 in Prelamin A Maturation by Douglas P. Corrigan The nuclear lamins form a karyoskeleton providing structural rigidity to the nucleus. One member of the lamin family, lamin A, is first synthesized as a 74 kDa precursor, prelamin A. Following the endopeptidase and methylation reactions which occur after farnesylation of the CAAX-box cysteine, there is a second endoproteolysis that occurs 15 amino acids upstream from the C-terminal farnesylated cysteine residue.
  • Expression Profiling of KLF4

    Expression Profiling of KLF4

    Expression Profiling of KLF4 AJCR0000006 Supplemental Data Figure S1. Snapshot of enriched gene sets identified by GSEA in Klf4-null MEFs. Figure S2. Snapshot of enriched gene sets identified by GSEA in wild type MEFs. 98 Am J Cancer Res 2011;1(1):85-97 Table S1: Functional Annotation Clustering of Genes Up-Regulated in Klf4 -Null MEFs ILLUMINA_ID Gene Symbol Gene Name (Description) P -value Fold-Change Cell Cycle 8.00E-03 ILMN_1217331 Mcm6 MINICHROMOSOME MAINTENANCE DEFICIENT 6 40.36 ILMN_2723931 E2f6 E2F TRANSCRIPTION FACTOR 6 26.8 ILMN_2724570 Mapk12 MITOGEN-ACTIVATED PROTEIN KINASE 12 22.19 ILMN_1218470 Cdk2 CYCLIN-DEPENDENT KINASE 2 9.32 ILMN_1234909 Tipin TIMELESS INTERACTING PROTEIN 5.3 ILMN_1212692 Mapk13 SAPK/ERK/KINASE 4 4.96 ILMN_2666690 Cul7 CULLIN 7 2.23 ILMN_2681776 Mapk6 MITOGEN ACTIVATED PROTEIN KINASE 4 2.11 ILMN_2652909 Ddit3 DNA-DAMAGE INDUCIBLE TRANSCRIPT 3 2.07 ILMN_2742152 Gadd45a GROWTH ARREST AND DNA-DAMAGE-INDUCIBLE 45 ALPHA 1.92 ILMN_1212787 Pttg1 PITUITARY TUMOR-TRANSFORMING 1 1.8 ILMN_1216721 Cdk5 CYCLIN-DEPENDENT KINASE 5 1.78 ILMN_1227009 Gas2l1 GROWTH ARREST-SPECIFIC 2 LIKE 1 1.74 ILMN_2663009 Rassf5 RAS ASSOCIATION (RALGDS/AF-6) DOMAIN FAMILY 5 1.64 ILMN_1220454 Anapc13 ANAPHASE PROMOTING COMPLEX SUBUNIT 13 1.61 ILMN_1216213 Incenp INNER CENTROMERE PROTEIN 1.56 ILMN_1256301 Rcc2 REGULATOR OF CHROMOSOME CONDENSATION 2 1.53 Extracellular Matrix 5.80E-06 ILMN_2735184 Col18a1 PROCOLLAGEN, TYPE XVIII, ALPHA 1 51.5 ILMN_1223997 Crtap CARTILAGE ASSOCIATED PROTEIN 32.74 ILMN_2753809 Mmp3 MATRIX METALLOPEPTIDASE
  • ZMPSTE24 Is Associated with Elevated Inflammation and Progerin Mrna

    ZMPSTE24 Is Associated with Elevated Inflammation and Progerin Mrna

    cells Article ZMPSTE24 Is Associated with Elevated Inflammation and Progerin mRNA 1, 1, 1 2 Moritz Messner y, Santhosh Kumar Ghadge y, Thomas Maurer , Michael Graber , Simon Staggl 1, Sarah Christine Maier 3, Gerhard Pölzl 1 and Marc-Michael Zaruba 1,* 1 Department of Internal Medicine III, Cardiology and Angiology, Medical University Innsbruck, 6020 Innsbruck, Austria; [email protected] (M.M.); [email protected] (S.K.G.); [email protected] (T.M.); [email protected] (S.S.); [email protected] (G.P.) 2 Department of Thoracic & Cardiac Surgery, Medical University Innsbruck, 6020 Innsbruck, Austria; [email protected] 3 Department of Medical Statistics, Informatics and Health Economics, Medical University Innsbruck, 6020 Innsbruck, Austria; [email protected] * Correspondence: [email protected]; Tel.: +0043-512-504-25621 Moritz Messner and Santhosh Kumar Ghadge contributed equally to this manuscript. y Received: 30 March 2020; Accepted: 27 August 2020; Published: 28 August 2020 Abstract: Lamins are important filaments forming the inner nuclear membrane. Lamin A is processed by zinc metalloproteinase (ZMPSTE24). Failure to cleave a truncated form of prelamin A—also called progerin—causes Hutchinson–Gilford progeria syndrome a well-known premature aging disease. Minor levels of progerin are readily expressed in the blood of healthy individuals due to alternative splicing. Previously, we found an association of increased progerin mRNA with overweight and chronic inflammation (hs-CRP). Here, we aimed to elucidate correlations of ZMPSTE24, lamin A/C and progerin with the inflammatory marker hs-CRP.
  • Supplementary Table S4. FGA Co-Expressed Gene List in LUAD

    Supplementary Table S4. FGA Co-Expressed Gene List in LUAD

    Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase
  • Neurodegeneration in Accelerated Aging

    Neurodegeneration in Accelerated Aging

    DOCTOR OF MEDICAL SCIENCE DANISH MEDICAL JOURNAL Neurodegeneration in Accelerated Aging Morten Scheibye-Knudsen This review has been accepted as a thesis together with 7 previously published pa- pers by the University of Copenhagen, October 16, 2014 and defended on January 14, 2016 Official opponents: Alexander Bürkle, University of Konstanz Lars Eide, University of Oslo Correspondence: Center for Healthy Aging, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen E-mail: [email protected] Dan Med J 2016;63(11):B5308 INTRODUCTION The global elderly population has been progressively increasing throughout the 20th century and this growth is projected to per- sist into the late 21st century resulting in 20% of the total world population being aged 65 or more by the year 2100 (Figure 1). 80% of the total cost of health care is accrued after 40 years of Figure 2. The phenotype of human aging. age where chronic diseases become prevalent [1, 2]. With an ex- that appear to regulate the aging process [4,5]. These include the ponential increase in health care costs, it follows that the chronic insulin and IGF-1 signaling cascades [4], protein synthesis and diseases that accumulate in an aging population poses a serious quality control [6], regulation of cell proliferation through factors socioeconomic problem. Finding treatments to age related dis- such as mTOR [7], stem cell maintenance 8 as well as mitochon- eases, therefore becomes increasingly more pertinent as the pop- drial preservation [9]. Most of these pathways are conserved ulation ages. Even more so since there appears to be a continu- through evolution and appear to regulate aging in many lower or- ous increase in the prevalence of chronic diseases in the aging ganisms.
  • Trichothiodystrophy

    Trichothiodystrophy

    Trichothiodystrophy Author: Doctor Alfredo Rossi1 and Doctor C. Cantisani. Creation date: June 2004 Scientific Editor: Prof Antonella Tosti 1Dipartimento di Malattie Cutanee-Veneree Chirurgia Plastica-Ricostruttiva, Università degli studi di Roma “La Sapienza” Abstract Keywords Definition Epidemiology Etiology Clinical description Diagnostic methods Prenatal diagnosis Management References Abstract Trichothiodystrophy (TTD) is a rare autosomal recessive genetic disorder characterized by abnormal synthesis of the sulphur containing keratins and consequently hair dysplasia, associated with numerous symptoms affecting mainly organs derived from the neuroectoderm. This phenotypic aspect is due to mutations in the DNA-dependent ATPase/helicase subunit of TFIIH, XPB and XPD. Abnormalities in excision repair of ultraviolet (UV)-damaged DNA are recognized in about half of the patients. The clinical appearance is characterized by brittle and fragile hair, congenital ichthyosis, nail and dental dysplasias, cataract, progeria-like face, growth and mental retardation. The abnormalities are usually obvious at birth, with variable clinical expression. The variants of TTD, depending on their different associations, are known by the initials BIDS, IBIDS, PIBIDS, SIBIDS, ONMRS, as well as the eponyms of the Pollit, Tay, Sabinas syndromes or Amish brittle hair. The exact prevalence of TTD is unknown, but appears to be rather uncommon. About 20 cases of PIBI(D)S have been reported in the literature. Up to 1991, clinical data of 15 cases with IBIDS were published. Prenatal diagnostic of TTD is available. There is no specific treatment. Keywords Brittle hair, photosensitivity, ichthyosis, BIDS, IBIDS, PIBIDS, SIBIDS, ONMRS, Tay-syndrome Definition tail pattern). They named it Trichothiodystrophy, Trichothiodystrophy (TTD) is a group of rare noticing also an increased Photosensitivity and autosomal recessive disorders with heterogenic Ichthyosis in these patients (PIBIDS).
  • 1. Progeria 101: Frequently Asked Questions

    1. Progeria 101: Frequently Asked Questions

    1. PROGERIA 101: FREQUENTLY ASKED QUESTIONS 1. Progeria 101: Frequently Asked Questions What is Hutchinson-Gilford Progeria Syndrome? What is PRF’s history and mission? What causes Progeria? How is Progeria diagnosed? Are there different types of Progeria? Is Progeria contagious or inherited? What is Hutchinson-Gilford Progeria Syndrome (HGPS or Progeria)? Progeria is also known as Hutchinson-Gilford Progeria Syndrome (HGPS). Genetic testing for It was first described in 1886 by Dr. Jonathan Hutchinson and in 1897 by Progeria can be Dr. Hastings Gilford. Progeria is a rare, fatal, “premature aging” syndrome. It’s called a syndrome performed from a because all the children have very similar symptoms that “go together”. The small sample of blood children have a remarkably similar appearance, even though Progeria affects children of all different ethnic backgrounds. Although most babies with (1-2 tsp) or sometimes Progeria are born looking healthy, they begin to display many characteristics from a sample of saliva. of accelerated aging by 18-24 months of age, or even earlier. Progeria signs include growth failure, loss of body fat and hair, skin changes, stiffness of joints, hip dislocation, generalized atherosclerosis, cardiovascular (heart) disease, and stroke. Children with Progeria die of atherosclerosis (heart disease) or stroke at an average age of 13 years (with a range of about 8-21 years). Remarkably, the intellect of children with Progeria is unaffected, and despite the physical changes in their young bodies, these extraordinary children are intelligent, courageous, and full of life. 1.2 THE PROGERIA HANDBOOK What is PRF’s history and mission? The Progeria Research Foundation (PRF) was established in the United States in 1999 by the parents of a child with Progeria, Drs.
  • Werner and Hutchinson–Gilford Progeria Syndromes: Mechanistic Basis of Human Progeroid Diseases

    Werner and Hutchinson–Gilford Progeria Syndromes: Mechanistic Basis of Human Progeroid Diseases

    REVIEWS MECHANISMS OF DISEASE Werner and Hutchinson–Gilford progeria syndromes: mechanistic basis of human progeroid diseases Brian A. Kudlow*¶, Brian K. Kennedy* and Raymond J. Monnat Jr‡§ Abstract | Progeroid syndromes have been the focus of intense research in part because they might provide a window into the pathology of normal ageing. Werner syndrome and Hutchinson–Gilford progeria syndrome are two of the best characterized human progeroid diseases. Mutated genes that are associated with these syndromes have been identified, mouse models of disease have been developed, and molecular studies have implicated decreased cell proliferation and altered DNA-damage responses as common causal mechanisms in the pathogenesis of both diseases. Progeroid syndromes are heritable human disorders with therefore termed segmental, as opposed to global, features that suggest premature ageing1. These syndromes progeroid syndromes. Among the segmental progeroid have been well characterized as clinical disease entities, syndromes, the syndromes that most closely recapitu- and in many instances the associated genes and causative late the features of human ageing are Werner syndrome mutations have been identified. The identification of (WS), Hutchinson–Gilford progeria syndrome (HGPS), genes that are associated with premature-ageing-like Cockayne syndrome, ataxia-telangiectasia, and the con- syndromes has increased our understanding of molecu- stitutional chromosomal disorders of Down, Klinefelter lar pathways that protect cell viability and function, and