Genetic Disorders of the Extracellular Matrix
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
The Skin in the Ehlers-Danlos Syndromes
EDS Global Learning Conference July 30-August 1, 2019 (Nashville) The Skin in the Ehlers-Danlos Syndromes Dr Nigel Burrows Consultant Dermatologist MD FRCP Department of Dermatology Addenbrooke’s Hospital Cambridge University NHS Foundation Trust Cambridge, UK No conflict of interests or disclosures Burrows, N: The Skin in EDS 1 EDS Global Learning Conference July 30-August 1, 2019 (Nashville) • Overview of skin and anatomy • Skin features in commoner EDS • Skin features in rarer EDS subtypes • Skin management The skin • Is useful organ to sustain life ØProtection - microorganisms, ultraviolet light, mechanical damage ØSensation ØAllows movement ØEndocrine - vitamin D production ØExcretion - sweat ØTemperature regulation Burrows, N: The Skin in EDS 2 EDS Global Learning Conference July 30-August 1, 2019 (Nashville) The skin • Is useful organ to sustain life • Provides a visual clue to diagnoses • Important for cultures and traditions • Ready material for research Skin Fun Facts • Largest organ in the body • In an average adult the skin weighs approx 5kg (11lbs) and covers 2m2 (21 sq ft) • 11 miles of blood vessels • The average person has about 300 million skin cells • More than half of the dust in your home is actually dead skin • Your skin is home to more than 1,000 species of bacteria Burrows, N: The Skin in EDS 3 EDS Global Learning Conference July 30-August 1, 2019 (Nashville) The skin has 3 main layers Within the Dermis Extracellular Matrix 1. Collagen 2. Elastic fibres 3. Ground Substances i) glycosaminoglycans, ii) proteoglycans, -
Vascular Phenotypes in Nonvascular Subtypes of the Ehlers-Danlos Syndrome: a Systematic Review
SYSTEMATIC REVIEW Official journal of the American College of Medical Genetics and Genomics Vascular phenotypes in nonvascular subtypes of the Ehlers-Danlos syndrome: a systematic review Sanne D’hondt, MSc1, Tim Van Damme, MD1 and Fransiska Malfait, MD, PhD1 Purpose: Within the spectrum of the Ehlers-Danlos syndromes (53%), frequently reported in musculocontractural and classical- (EDS), vascular complications are usually associated with the like EDS; intracranial hemorrhages (18%), with a high risk in vascular subtype of EDS. Vascular complications are also observed dermatosparaxis EDS; and arterial dissections (16%), frequently in other EDS subtypes, but the reports are anecdotal and the reported in kyphoscoliotic and classical EDS. Other, more minor, information is dispersed. To better document the nature of vascular vascular complications were reported in cardiac-valvular, arthro- complications among “nonvascular” EDS subtypes, we performed chalasia, spondylodysplastic, and periodontal EDS. a systematic review. Conclusion: Potentially life-threatening vascular complications are Methods: We queried three databases for English-language a rare but important finding in several nonvascular EDS sub- studies from inception until May 2017, documenting both types, highlighting a need for more systematic documentation. This phenotypes and genotypes of patients with nonvascular EDS review will help familiarize clinicians with the spectrum of vascular subtypes. The outcome included the number and nature of vascular complications in EDS and guide follow-up and management. complications. Genet Med advance online publication 5 October 2017 Results: A total of 112 papers were included and data were collected from 467 patients, of whom 77 presented with a vascular Key Words: connective tissue disorder; Ehlers-Danlos syndrome; phenotype. -
Phenotype and Response to Growth Hormone Therapy in Siblings with B4GALT7 Deficiency T ⁎ Carla Sandler-Wilsona, Jennifer A
Bone 124 (2019) 14–21 Contents lists available at ScienceDirect Bone journal homepage: www.elsevier.com/locate/bone Case Report Phenotype and response to growth hormone therapy in siblings with B4GALT7 deficiency T ⁎ Carla Sandler-Wilsona, Jennifer A. Wambacha, , Bess A. Marshalla,b, Daniel J. Wegnera, William McAlisterc, F. Sessions Colea,b, Marwan Shinawia a Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO 63110, USA b Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO 63110, USA c Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, MO 63110, USA ARTICLE INFO ABSTRACT Keywords: B4GALT7 encodes beta-1,4-galactosyltransferase which links glycosaminoglycans to proteoglycans in connective B4GALT7 tissues. Rare, biallelic variants in B4GALT7 have been associated with spondylodysplastic Ehlers-Danlos and Spondylodysplastic Ehlers-Danlos syndrome Larsen of Reunion Island syndromes. Thirty patients with B4GALT7-related disorders have been reported to date Larsen of Reunion Island syndrome with phenotypic variability. Using whole exome sequencing, we identified male and female siblings with bial- Growth hormone lelic, pathogenic B4GALT7 variants and phenotypic features of spondylodysplastic Ehlers-Danlos syndrome as Proteoglycan well as previously unreported skeletal characteristics. We also provide detailed radiological -
Pathophysiological Significance of Dermatan Sulfate Proteoglycans Revealed by Human Genetic Disorders
Title Pathophysiological Significance of Dermatan Sulfate Proteoglycans Revealed by Human Genetic Disorders Author(s) Mizumoto, Shuji; Kosho, Tomoki; Yamada, Shuhei; Sugahara, Kazuyuki Pharmaceuticals, 10(2), 34 Citation https://doi.org/10.3390/ph10020034 Issue Date 2017-06 Doc URL http://hdl.handle.net/2115/67053 Rights(URL) http://creativecommons.org/licenses/by/4.0/ Type article File Information pharmaceuticals10-2 34.pdf Instructions for use Hokkaido University Collection of Scholarly and Academic Papers : HUSCAP pharmaceuticals Review Pathophysiological Significance of Dermatan Sulfate Proteoglycans Revealed by Human Genetic Disorders Shuji Mizumoto 1,*, Tomoki Kosho 2, Shuhei Yamada 1 and Kazuyuki Sugahara 1,* 1 Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, Japan; [email protected] 2 Center for Medical Genetics, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan; [email protected] * Correspondence: [email protected] (S.M.); [email protected] (K.S.); Tel.: +81-52-839-2652 Academic Editor: Barbara Mulloy Received: 22 February 2017; Accepted: 24 March 2017; Published: 27 March 2017 Abstract: The indispensable roles of dermatan sulfate-proteoglycans (DS-PGs) have been demonstrated in various biological events including construction of the extracellular matrix and cell signaling through interactions with collagen and transforming growth factor-β, respectively. Defects in the core proteins of DS-PGs such as decorin and -
Classification, Nosology and Diagnostics of Ehlers-Danlos Syndrome
J.Biomed.Transl.Res ISSN: 2503-2178 Copyright©2019 by Faculty of Medicine Diponegoro University and Indonesian Medical Association, Central Java Region Review Articles Classification, nosology and diagnostics of Ehlers-Danlos syndrome Ben C.J. Hamel* Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands Article Info Abstract History Ehlers-Danlos syndrome (EDS) comprises a group of heritable connective tissue Received : 23 March 2019 disorders which has as cardinal features varying degrees of skin hyperextensibility, Accepted : 10 Oct 2019 joint hypermobility, easy bruising and skin fragility. The 2017 New York nosology Available : 31 Dec 2019 distinguishes 13 types of EDS, which all, except hypermobile EDS, have a known molecular basis. Hypermobile EDS is recognized as a common and often disabling disorder, incorporating benign joint hypermobility syndrome. EDS needs to be differentiated from other connective tissue disorders, in particular Marfan syndrome, Loeys-Dietz syndrome and cutis laxa. The frequent types of EDS can be diagnosed after careful history taking and clinical examination, but for definite diagnosis, molecular confirmation is needed in all types. Management for EDS patients preferably is provided by multidisciplinary teams in expertise centres. After diagnosing EDS, genetic counselling is an essential part of the management of patients and their family. Keywords : Ehlers-Danlos syndrome; classification; diagnosis Permalink/ DOI: https://doi.org/10.14710/jbtr.v5i2.4531 INTRODUCTION EDS comprises a clinically and genetically The most striking changes were: heterogeneous group of heritable connective tissue - incorporating EDS types which were published disorders (HCTD), mainly characterized by a variable since the Villefranche nosology, leading to a total degree of generalized joint hypermobility, skin number of 13 types.4 hyperextensibility, easy bruising and skin fragility. -
Understanding the Basis of Ehlers–Danlos Syndrome in the Era of the Next-Generation Sequencing
Archives of Dermatological Research (2019) 311:265–275 https://doi.org/10.1007/s00403-019-01894-0 REVIEW Understanding the basis of Ehlers–Danlos syndrome in the era of the next-generation sequencing Francesca Cortini1,2 · Chiara Villa3 · Barbara Marinelli1 · Romina Combi3 · Angela Cecilia Pesatori1 · Alessandra Bassotti4 Received: 29 July 2018 / Revised: 26 November 2018 / Accepted: 12 February 2019 / Published online: 2 March 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Ehlers–Danlos syndrome (EDS) is a clinically and genetically heterogeneous group of heritable connective tissue disorders (HCTDs) defined by joint laxity, skin alterations, and joint hypermobility. The latest EDS classification recognized 13 sub- types in which the clinical and genetic phenotypes are often overlapping, making the diagnosis rather difficult and strength- ening the importance of the molecular diagnostic confirmation. New genetic techniques such as next-generation sequencing (NGS) gave the opportunity to identify the genetic bases of unresolved EDS types and support clinical counseling. To date, the molecular defects have been identified in 19 genes, mainly in those encoding collagen, its modifying enzymes or other constituents of the extracellular matrix (ECM). In this review we summarize the contribution of NGS technologies to the current knowledge of the genetic background in different EDS subtypes. Keywords Ehlers–Danlos syndrome · Heterogeneity · Heritable connective tissue disorders Introduction in 1988, represents the first attempt to classify EDS, recog- nizing 11 EDS subtypes [4], defined by Roman numerals and Ehlers–Danlos syndrome (EDS) comprises a clinically and classified according to clinical findings and the inheritance heterogeneous group of heritable connective tissue disor- pattern. -
Blueprint Genetics Comprehensive Growth Disorders / Skeletal
Comprehensive Growth Disorders / Skeletal Dysplasias and Disorders Panel Test code: MA4301 Is a 374 gene panel that includes assessment of non-coding variants. This panel covers the majority of the genes listed in the Nosology 2015 (PMID: 26394607) and all genes in our Malformation category that cause growth retardation, short stature or skeletal dysplasia and is therefore a powerful diagnostic tool. It is ideal for patients suspected to have a syndromic or an isolated growth disorder or a skeletal dysplasia. About Comprehensive Growth Disorders / Skeletal Dysplasias and Disorders This panel covers a broad spectrum of diseases associated with growth retardation, short stature or skeletal dysplasia. Many of these conditions have overlapping features which can make clinical diagnosis a challenge. Genetic diagnostics is therefore the most efficient way to subtype the diseases and enable individualized treatment and management decisions. Moreover, detection of causative mutations establishes the mode of inheritance in the family which is essential for informed genetic counseling. For additional information regarding the conditions tested on this panel, please refer to the National Organization for Rare Disorders and / or GeneReviews. Availability 4 weeks Gene Set Description Genes in the Comprehensive Growth Disorders / Skeletal Dysplasias and Disorders Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD ACAN# Spondyloepimetaphyseal dysplasia, aggrecan type, AD/AR 20 56 Spondyloepiphyseal dysplasia, Kimberley -
Blueprint Genetics Comprehensive Skeletal Dysplasias and Disorders
Comprehensive Skeletal Dysplasias and Disorders Panel Test code: MA3301 Is a 251 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion of disorders involving the skeletal system. About Comprehensive Skeletal Dysplasias and Disorders This panel covers a broad spectrum of skeletal disorders including common and rare skeletal dysplasias (eg. achondroplasia, COL2A1 related dysplasias, diastrophic dysplasia, various types of spondylo-metaphyseal dysplasias), various ciliopathies with skeletal involvement (eg. short rib-polydactylies, asphyxiating thoracic dysplasia dysplasias and Ellis-van Creveld syndrome), various subtypes of osteogenesis imperfecta, campomelic dysplasia, slender bone dysplasias, dysplasias with multiple joint dislocations, chondrodysplasia punctata group of disorders, neonatal osteosclerotic dysplasias, osteopetrosis and related disorders, abnormal mineralization group of disorders (eg hypopohosphatasia), osteolysis group of disorders, disorders with disorganized development of skeletal components, overgrowth syndromes with skeletal involvement, craniosynostosis syndromes, dysostoses with predominant craniofacial involvement, dysostoses with predominant vertebral involvement, patellar dysostoses, brachydactylies, some disorders with limb hypoplasia-reduction defects, ectrodactyly with and without other manifestations, polydactyly-syndactyly-triphalangism group of disorders, and disorders with defects in joint formation and synostoses. Availability 4 weeks Gene Set Description -
(12) Patent Application Publication (10) Pub. No.: US 2006/0134109 A1 Gaitanaris Et Al
US 2006O134109A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0134109 A1 Gaitanaris et al. (43) Pub. Date: Jun. 22, 2006 (54) GPROTEIN COUPLED RECEPTORS AND in-part of application No. 60/461.329, filed on Apr. 9. USES THEREOF 2003. (75) Inventors: George A. Gaitanaris, Seattle, WA Publication Classification (US); John E. Bergmann, Mercer Island, WA (US); Alexander Gragerov, (51) Int. Cl. Seattle, WA (US); John Hohmann, La CI2O I/68 (2006.01) Conner, WA (US); Fusheng Li, Seattle, C7H 2L/04 (2006.01) WA (US); Linda Madisen, Seattle, WA (US); Kellie L. McIlwain, Renton, WA CI2P 2/06 (2006.01) (US); Maria N. Pavlova, Seattle, WA A 6LX 39/395 (2006.01) (US); Demitri Vassilatis, Seattle, WA C07K I4/705 (2006.01) (US); Hongkui Zeng, Shoreline, WA (52) U.S. Cl. ......................... 424/143.1: 435/6: 435/69.1; 435/320.1; 435/325; 530/350; (US) 536/23.5 Correspondence Address: SEED INTELLECTUAL PROPERTY LAW GROUP PLLC (57) ABSTRACT 701 FIFTHAVE SUTE 63OO The present invention provides GPCR polypeptides and SEATTLE, WA 98104-7092 (US) polynucleotides, recombinant materials, and transgenic (73) Assignee: Nura Inc., Seattle, WA (US) mice, as well as methods for their production. The polypep tides and polynucleotides are useful, for example, in meth (21) Appl. No.: 10/527,265 ods of diagnosis and treatment of diseases and disorders. The invention also provides methods for identifying com (22) PCT Fed: Sep. 9, 2003 pounds (e.g., agonists or antagonists) using the GPCR polypeptides and polynucleotides of the invention, and for (86) PCT No.: PCT/USO3/28226 treating conditions associated with GPCR dysfunction with the GPCR polypeptides, polynucleotides, or identified com Related U.S. -
Recessive Multiple Epiphyseal Dysplasia – Clinical Characteristics Caused by T Rare Compound Heterozygous SLC26A2 Genotypes Mehran Kausara,B, Riikka E
European Journal of Medical Genetics 62 (2019) 103573 Contents lists available at ScienceDirect European Journal of Medical Genetics journal homepage: www.elsevier.com/locate/ejmg Recessive multiple epiphyseal dysplasia – Clinical characteristics caused by T rare compound heterozygous SLC26A2 genotypes Mehran Kausara,b, Riikka E. Mäkitieb, Sanna Toiviainen-Saloc, Jaakko Ignatiusd, Mariam Aneesa, ∗ Outi Mäkitieb,e,f,g, a Department of Biochemistry, Quaid-i-Azam University, Islamabad, Pakistan b Folkhälsan Institute of Genetics and University of Helsinki, Helsinki, Finland c Department of Pediatric Radiology, HUS Medical Imaging Centre, University of Helsinki and Helsinki University Hospital, Helsinki, Finland d Department of Clinical Genetics, University of Turku and Turku University Hospital, Turku, Finland e Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland f Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden g Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden ARTICLE INFO ABSTRACT Keywords: Pathogenic sequence variants in the solute carrier family 26 member 2 (SLC26A2) gene result in lethal rMED (achondrogenesis Ib and atelosteogenesis II) and non-lethal (diastrophic dysplasia and recessive multiple epi- Chondrodysplasia physeal dysplasia, rMED) chondrodysplasias. We report on two new patients with rMED and very rare compound SLC26A2 heterozygous mutation combinations in non-consanguineous families. Patient I presented in childhood with Double-layer patella waddling gait and joint stiffness. Radiographs showed epiphyseal changes, bilateral coxa plana–deformity and Robin sequence knee valgus deformity, for which he underwent surgeries. At present 33 years his height is 165 cm. Patient II presented with cleft palate, small jaw, short limbs, underdeveloped thumbs and on radiographs, cervical ky- phosis with an underdeveloped C4. -
A Diagnostic Approach to Skeletal Dysplasias
CHAPTER 16 A Diagnostic Approach to Skeletal Dysplasias SHEILA UNGER,ANDREA SUPERTI-FURGA,and DAVID L. RIMOIN [AU1] INTRODUCTION and outlines some of the more important radiographic ®ndings. The skeletal dysplasias are disorders characterized by developmental abnormalities of the skeleton. They form a large heterogeneous group and range in severity from BACKGROUND precocious osteoarthropathy to perinatal lethality [1,2]. Disproportionate short stature is the most frequent clin- Each skeletal dysplasia is rare, but collectively the ical complication but is not uniformly present. There are birth incidence is approximately 1/5000 [4,5]. The ori- more than 100 recognized forms of skeletal dysplasia, ginal classi®cation of skeletal dysplasias was quite sim- which can make determining a speci®c diagnosis dif®cult plistic. Patients were categorized as either short trunked [1]. This process is further complicated by the rarity of (Morquio syndrome) or short limbed (achondroplasia) the individual conditions. The establishment of a precise [6] (Fig. 1). As awareness of these conditions grew, their diagnosis is important for numerous reasons, including numbers expanded to more than 200 and this gave rise to prediction of adult height, accurate recurrence risk, pre- an unwieldy and complicated nomenclature [7]. In 1977, natal diagnosis in future pregnancies, and, most import- N. Butler made the prophetic statement that ``in recent ant, for proper clinical management. Once a skeletal years, attempts to classify bone dysplasias have been dysplasia is suspected, clinical and radiographic indica- more proli®c than enduring'' [8]. The advent of molecu- tors, along with more speci®c biochemical and molecular lar testing allowed the grouping of some dysplasias into tests, are employed to determine the underlying diagno- families. -
Musculo-Contractural Ehlers-Danlos Syndrome
Musculo-contractural Ehlers-Danlos syndrome (former EDS type VIB) and adducted thumb clubfoot syndrome (ATCS) represent a single clinical entity caused by mutations in the dermatan-4-sulfotransferase 1 encoding CHST14 gene. Fransiska Malfait, Delfien Syx, Philip Vlummens, Sofie Symoens, Sheela Nampoothiri, Trinh Hermanns-Lê, Lut van Laer, Anne Depaepe To cite this version: Fransiska Malfait, Delfien Syx, Philip Vlummens, Sofie Symoens, Sheela Nampoothiri, et al.. Musculo- contractural Ehlers-Danlos syndrome (former EDS type VIB) and adducted thumb clubfoot syndrome (ATCS) represent a single clinical entity caused by mutations in the dermatan-4-sulfotransferase 1 encoding CHST14 gene.. Human Mutation, Wiley, 2010, 31 (11), pp.1233. 10.1002/humu.21355. hal-00599478 HAL Id: hal-00599478 https://hal.archives-ouvertes.fr/hal-00599478 Submitted on 10 Jun 2011 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Human Mutation Musculo-contractural Ehlers-Danlos syndrome (former EDS type VIB) and adducted thumb clubfoot syndrome (ATCS) represent a single clinical