DOCSLIB.ORG

Genetic Testing Services and Support, from Preconception to Prenatal the Way Many Think About Carrier Screening Is Changing

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Genetic Testing Services and Support, from Preconception to Prenatal the Way Many Think About Carrier Screening Is Changing Genetic testing services and support, from preconception to prenatal The way many think about carrier screening is changing. Carrier screening, once thought to be a test primarily for specific ethnic groups, is now often recommended for every patient. The American Congress of Obstetricians and Gynecologists (ACOG) recently updated its recommendations, stating that carrier screening for spinal muscular atrophy (SMA), in addition to cystic fibrosis (CF), "should be offered to all women who are considering pregnancy or are currently pregnant."7 COMPREHENSIVE, VERSATILE, COVERING WHAT MATTERS Inheritest® provides carrier screening for more than 110 severe disorders that can cause cognitive or physical impairment and/or require surgical or medical intervention. Selected to focus on severe disorders of childhood onset, and to meet ACOG and the American College of Medical Genetics and Genomics (ACMG) criteria, many of the disorders share a recommendation for early intervention. Inheritest offers multiple panels to suit the diverse needs of your patients: Focuses on mutations for CF, SMA, and fragile X syndrome, with the following carrier risks: CORE PANEL CF: as high as 1 in 248 SMA: as high as 1 in 479 Fragile X syndrome: approximately 3 GENES (varies by ethnicity) (varies by ethnicity) 1 in 259 females (all ethnicities)10 SOCIETY-GUIDED PANEL Includes mutations for more than 13 disorders listed in ACOG and/or ACMG recommendations 14 GENES ASHKENAZI JEWISH Enhanced panel includes mutations for more than 40 disorders relevant to patients of Ashkenazi PANEL 48 GENES Jewish descent COMPREHENSIVE Includes mutations for more than 110 disorders across 144 different genes—includes all disorders in PANEL 144 GENES Core, Society-guided, and Ashkenazi Jewish panels THE CASE FOR EXPANDED CARRIER SCREENING While some providers may only screen for CF or select screening based on ethnicity, the case for more comprehensive screening is becoming clear. According to a bulletin from the World Health Organization, the global prevalence at 80% birth of all single-gene disorders is about 10 per 1000.1 Genes not included in ACOG and ACMG Our internal laboratory data also supports the case for more comprehensive recommendations screening. In screening over a thousand patients with the Comprehensive panel, our data showed that focusing only on disorders listed in ACOG/ACMG 2 20% recommendations can result in a significant number of missed carriers (see figure 1). Genes included in ACOG/ Of the disorders a Comprehensive panel can identify:* ACMG recommendations Figure 1: percentage of patients who screened positive for a can result in severe early onset, increased childhood mortality, or mutation in at least one gene in the shortened lifespan Inheritest Comprehensive panel 115 78 may cause intellectual disability are metabolic disorders that may have treatment benefit with early 77 medical intervention may cause loss of vision/ eye problems in affected individuals—early 62 identification could be beneficial may cause deafness/ hearing loss—early identification could be 39 beneficial are X-linked, meaning only the mother has to be a carrier for the child to 6 be at risk Some disorders will have characteristics of multiple categories. ANCESTRY AND FAMILY HISTORY CAN BE A MYSTERY An absence of disorders in a patient’s family can be an insufficient guide for targeted screening. For example, more than 80% of infants with CF are born to families with no prior family history.5 In addition, early studies estimated that each person carries three to five mutations, which, if passed along in a pregnancy, could lead to a genetic disorder.6 *Based on information on the relevant disorders compiled from Genetics Home Reference and GARD.3, 4 †Next-generation sequencing is used for the Comprehensive, Ashkenazi Jewish, and Society-guided panels. PCR with reflex to Southern blot is used for fragile X syndrome analysis, quantitative PCR analysis is used for SMA analysis and deletion/duplication analysis is used for alpha-thalassemia analysis. While all panels include CF analysis, the Core panel uses a bead-based array that identifies 97 common CF mutations. BEYOND NGS TO DELIVER FOCUSED PARTNER TESTING PRENATAL DIAGNOSIS GREATER ACCURACY If your patient’s result is positive, Additionally, once an at-risk pregnancy Integrated Genetics can offer her is identified, we can perform prenatal Inheritest Carrier Screen uses next- partner full gene sequencing for any diagnostic testing—for any of the generation sequencing (NGS)† to autosomal recessive gene in the disorders in the Inheritest panels—to capture a broad spectrum of mutations, Inheritest panels (except SMA, for deliver insights regarding the baby's including rare variants, with Sanger which we offer partners SMN1 copy condition. sequencing and other appropriate number analysis). technologies to confirm positive Where some testing service providers results and deliver optimal sensitivity Full gene sequencing detects are unable to offer single gene and specificity. disease-causing variants as well as testing, VUS identification, or prenatal variants of uncertain significance, to diagnosis—sometimes resulting in identify a greater number of time-consuming retesting—Integrated potentially at-risk pregnancies. Genetics offers a continuum of care for patients that can both save time and reduce anxiety. Inheritest® Core panel Inheritest® Ashkenazi Jewish panel Cystic fibrosis (97 mutations) Abetalipoproteinemia Glycogen storage disease type Ia Spinal muscular atrophy NEW Alpha-thalassemia NEW Glycogen storage disease type III Fragile X syndrome (females only) Alport syndrome, COL4A3-related Joubert syndrome 2 Arthrogryposis, mental retardation, and Maple syrup urine disease type 1A seizures (AMRS) Inheritest® Society-guided Maple syrup urine disease type 1B panel NEW Ataxia-telangiectasia NEW Metachromatic leukodystrophy NEW Alpha-thalassemia Bardet-Biedl syndrome, BBS2-related Mucolipidosis type IV Beta hemoglobinopathy; includes NEW Beta hemoglobinopathy; includes sickle cell disease, hemoglobins C, sickle cell disease, hemoglobins C, D, E, Multiple sulphatase deficiency D, E, and O, and beta thalassemias and O, and beta thalassemias Bloom syndrome Nemaline myopathy, NEB-related Bloom syndrome Canavan disease Niemann-Pick disease types A and B Canavan disease Phenylalanine hydroxylase Cystic fibrosis NEW Carnitine palmitoyltransferase II deficiency, includes phenylketonuria deficiency (PKU) Familial dysautonomia Congenital amegakaryocytic Phosphoglycerate dehydrogenase thrombocytopenia Fanconi anemia group C deficiency,PHGDH -related Congenital disorder of glycosylation Polycystic kidney disease, autosomal type 1a Fragile X syndrome (females only) recessive Cystic fibrosis Gaucher disease Retinitis pigmentosa 59 NEW Cystinosis Mucolipidosis type IV Smith-Lemli-Opitz syndrome Dihydrolipoamide dehydrogenase Niemann-Pick disease types A deficiency Spinal muscular atrophy and B Tay-Sachs disease Spinal muscular atrophy Ehlers-Danlos syndrome type VIIC Tyrosinemia type 1 Tay-Sachs disease Familial dysautonomia Familial hyperinsulinism, Usher syndrome type IF ABCC8-related Usher syndrome type IIIA NEW Familial Mediterranean fever Walker-Warburg syndrome, FKTN- Fanconi anemia group C related Fragile X syndrome (females only) Wilson disease Zellweger spectrum disorder, PEX2- Galactosemia, GALT-related related NEW Zellweger spectrum disorder, Gaucher disease PEX6-related Inheritest® Comprehensive panel Abetalipoproteinemia Familial Mediterranean fever Metachromatic leukodystrophy Primary hyperoxaluria type 2 Adenosine deaminase deficiency Familial dysautonomia Methylmalonic acidemia, MMAA- Propionic acidemia, PCCA-related related Alpha-mannosidosis Familial hyperinsulinism, ABCC8- Propionic acidemia, PCCB -related Methylmalonic acidemia, MMAB NEW Alpha-thalassemia related -related Pyruvate dehydrogenase deficiency, Alport syndrome, COL4A3-related Fanconi anemia group C PDHA1-related Methylmalonic acidemia, MUT-related Andermann syndrome Fragile X syndrome (females only) Mitochondrial acetoacetyl-CoA Retinitis pigmentosa 59 Argininosuccinic aciduria thiolase deficiency Fucosidosis Rhizomelic chondrodysplasia Arthrogryposis, mental retardation, Mucolipidosis type II and III, GNPTAB- punctata type 1 and seizures (AMRS) GM1 gangliosidosis and related mucopolysaccharidosis type IVB Salla disease Aspartylglucosaminuria Mucolipidosis type IV GRACILE syndrome Sandhoff disease Ataxia with vitamin E deficiency Mucopolysaccharidosis type I Galactosemia, GALT-related Sialidosis Ataxia-telangiectasia Mucopolysaccharidosis type II Galactosialidosis Sjogren-Larsson syndrome Autosomal recessive spastic ataxia of Mucopolysaccharidosis type IIIA Charlevoix-Saguenay (ARSACS) Smith-Lemli-Opitz syndrome Gaucher disease Mucopolysaccharidosis type IIIB Bardet-Biedl syndrome, BBS1-related Spinal muscular atrophy Glutaric acidemia type 1 Mucopolysaccharidosis type IIIC Bardet-Biedl syndrome, BBS10- related Mucopolysaccharidosis type IIID Sulfate transporter-related Glutathione synthetase deficiency osteochondrodysplasias, includes Bardet-Biedl syndrome, BBS2-related Mucopolysaccharidosis type IV A achondrogenesis type 1B, Glycine encephalopathy, AMT-related atelosteogenesis type 2, diastrophic Beta hemoglobinopathy, includes Mucopolysaccharidosis type VI dysplasia, and recessive multiple sickle cell disease, hemoglobins C, D, Glycine encephalopathy, GLDC- epiphyseal dysplasia E, and O, and beta thalassemias related Mucopolysaccharidosis type VII Systemic
Load more

Recommended publications
  • The Counsyl Foresight™ Carrier Screen
    The Counsyl Foresight™ Carrier Screen 180 Kimball Way | South San Francisco, CA 94080 www.counsyl.com | [email protected] | (888) COUNSYL The Counsyl Foresight Carrier Screen - Disease Reference Book 11-beta-hydroxylase-deficient Congenital Adrenal Hyperplasia .................................................................................................................................................................................... 8 21-hydroxylase-deficient Congenital Adrenal Hyperplasia ...........................................................................................................................................................................................10 6-pyruvoyl-tetrahydropterin Synthase Deficiency ..........................................................................................................................................................................................................12 ABCC8-related Hyperinsulinism........................................................................................................................................................................................................................................ 14 Adenosine Deaminase Deficiency .................................................................................................................................................................................................................................... 16 Alpha Thalassemia.............................................................................................................................................................................................................................................................
    [Show full text]
  • Disease Reference Book
    The Counsyl Foresight™ Carrier Screen 180 Kimball Way | South San Francisco, CA 94080 www.counsyl.com | [email protected] | (888) COUNSYL The Counsyl Foresight Carrier Screen - Disease Reference Book 11-beta-hydroxylase-deficient Congenital Adrenal Hyperplasia .................................................................................................................................................................................... 8 21-hydroxylase-deficient Congenital Adrenal Hyperplasia ...........................................................................................................................................................................................10 6-pyruvoyl-tetrahydropterin Synthase Deficiency ..........................................................................................................................................................................................................12 ABCC8-related Hyperinsulinism........................................................................................................................................................................................................................................ 14 Adenosine Deaminase Deficiency .................................................................................................................................................................................................................................... 16 Alpha Thalassemia.............................................................................................................................................................................................................................................................
    [Show full text]
  • Alport Syndrome of the European Dialysis Population Suffers from AS [26], and Simi- Lar Figures Have Been Found in Other Series
    DOCTOR OF MEDICAL SCIENCE Patients with AS constitute 2.3% (11/476) of the renal transplant population at the Mayo Clinic [24], and 1.3% of 1,000 consecutive kidney transplant patients from Sweden [25]. Approximately 0.56% Alport syndrome of the European dialysis population suffers from AS [26], and simi- lar figures have been found in other series. AS accounts for 18% of Molecular genetic aspects the patients undergoing dialysis or having received a kidney graft in 2003 in French Polynesia [27]. A common founder mutation was in Jens Michael Hertz this area. In Denmark, the percentage of patients with AS among all patients starting treatment for ESRD ranges from 0 to 1.21% (mean: 0.42%) in a twelve year period from 1990 to 2001 (Danish National This review has been accepted as a thesis together with nine previously pub- Registry. Report on Dialysis and Transplantation in Denmark 2001). lished papers by the University of Aarhus, February 5, 2009, and defended on This is probably an underestimate due to the difficulties of establish- May 15, 2009. ing the diagnosis. Department of Clinical Genetics, Aarhus University Hospital, and Faculty of Health Sciences, Aarhus University, Denmark. 1.3 CLINICAL FEATURES OF X-LINKED AS Correspondence: Klinisk Genetisk Afdeling, Århus Sygehus, Århus Univer- 1.3.1 Renal features sitetshospital, Nørrebrogade 44, 8000 Århus C, Denmark. AS in its classic form is a hereditary nephropathy associated with E-mail: [email protected] sensorineural hearing loss and ocular manifestations. The charac- Official opponents: Lisbeth Tranebjærg, Allan Meldgaard Lund, and Torben teristic renal features in AS are persistent microscopic hematuria ap- F.
    [Show full text]
  • Its Place Among Other Genetic Causes of Renal Disease
    J Am Soc Nephrol 13: S126–S129, 2002 Anderson-Fabry Disease: Its Place among Other Genetic Causes of Renal Disease JEAN-PIERRE GRU¨ NFELD,* DOMINIQUE CHAUVEAU,* and MICHELINE LE´ VY† *Service of Nephrology, Hoˆpital Necker, Paris, France; †INSERM U 535, Baˆtiment Gregory Pincus, Kremlin- Biceˆtre, France. In the last two decades, decisive advances have been made in Nephropathic cystinosis, first described in 1903, is an auto- the field of human genetics, including renal genetics. The somal recessive disorder characterized by the intra-lysosomal responsible genes have been mapped and then identified in accumulation of cystine. It is caused by a defect in the transport most monogenic renal disorders by using positional cloning of cystine out of the lysosome, a process mediated by a carrier and/or candidate gene approaches. These approaches have that remained unidentified for several decades. However, an been extremely efficient since the number of identified genetic important management step was devised in 1976, before the diseases has increased exponentially over the last 5 years. The biochemical defect was characterized in 1982. Indeed cysteam- data derived from the Human Genome Project will enable a ine, an aminothiol, reacts with cystine to form cysteine-cys- more rapid identification of the genes involved in the remain- teamine mixed disulfide that can readily exit the cystinotic ing “orphan” inherited renal diseases, provided their pheno- lysosome. This drug, if used early and in high doses, retards the types are well characterized. We have entered the post-gene progression of cystinosis in affected subjects by reducing intra- era. What is/are the function(s) of these genes? What are the lysosomal cystine concentrations.
    [Show full text]
  • Genetic Disorder
    Genetic disorder Single gene disorder Prevalence of some single gene disorders[citation needed] A single gene disorder is the result of a single mutated gene. Disorder Prevalence (approximate) There are estimated to be over 4000 human diseases caused Autosomal dominant by single gene defects. Single gene disorders can be passed Familial hypercholesterolemia 1 in 500 on to subsequent generations in several ways. Genomic Polycystic kidney disease 1 in 1250 imprinting and uniparental disomy, however, may affect Hereditary spherocytosis 1 in 5,000 inheritance patterns. The divisions between recessive [2] Marfan syndrome 1 in 4,000 and dominant types are not "hard and fast" although the [3] Huntington disease 1 in 15,000 divisions between autosomal and X-linked types are (since Autosomal recessive the latter types are distinguished purely based on 1 in 625 the chromosomal location of Sickle cell anemia the gene). For example, (African Americans) achondroplasia is typically 1 in 2,000 considered a dominant Cystic fibrosis disorder, but children with two (Caucasians) genes for achondroplasia have a severe skeletal disorder that 1 in 3,000 Tay-Sachs disease achondroplasics could be (American Jews) viewed as carriers of. Sickle- cell anemia is also considered a Phenylketonuria 1 in 12,000 recessive condition, but heterozygous carriers have Mucopolysaccharidoses 1 in 25,000 increased immunity to malaria in early childhood, which could Glycogen storage diseases 1 in 50,000 be described as a related [citation needed] dominant condition. Galactosemia
    [Show full text]
  • Soonerstart Automatic Qualifying Syndromes and Conditions
    SoonerStart Automatic Qualifying Syndromes and Conditions - Appendix O Abetalipoproteinemia Acanthocytosis (see Abetalipoproteinemia) Accutane, Fetal Effects of (see Fetal Retinoid Syndrome) Acidemia, 2-Oxoglutaric Acidemia, Glutaric I Acidemia, Isovaleric Acidemia, Methylmalonic Acidemia, Propionic Aciduria, 3-Methylglutaconic Type II Aciduria, Argininosuccinic Acoustic-Cervico-Oculo Syndrome (see Cervico-Oculo-Acoustic Syndrome) Acrocephalopolysyndactyly Type II Acrocephalosyndactyly Type I Acrodysostosis Acrofacial Dysostosis, Nager Type Adams-Oliver Syndrome (see Limb and Scalp Defects, Adams-Oliver Type) Adrenoleukodystrophy, Neonatal (see Cerebro-Hepato-Renal Syndrome) Aglossia Congenita (see Hypoglossia-Hypodactylia) Aicardi Syndrome AIDS Infection (see Fetal Acquired Immune Deficiency Syndrome) Alaninuria (see Pyruvate Dehydrogenase Deficiency) Albers-Schonberg Disease (see Osteopetrosis, Malignant Recessive) Albinism, Ocular (includes Autosomal Recessive Type) Albinism, Oculocutaneous, Brown Type (Type IV) Albinism, Oculocutaneous, Tyrosinase Negative (Type IA) Albinism, Oculocutaneous, Tyrosinase Positive (Type II) Albinism, Oculocutaneous, Yellow Mutant (Type IB) Albinism-Black Locks-Deafness Albright Hereditary Osteodystrophy (see Parathyroid Hormone Resistance) Alexander Disease Alopecia - Mental Retardation Alpers Disease Alpha 1,4 - Glucosidase Deficiency (see Glycogenosis, Type IIA) Alpha-L-Fucosidase Deficiency (see Fucosidosis) Alport Syndrome (see Nephritis-Deafness, Hereditary Type) Amaurosis (see Blindness) Amaurosis
    [Show full text]
  • X Inactivation, Female Mosaicism, and Sex Differences in Renal Diseases
    BRIEF REVIEW www.jasn.org X Inactivation, Female Mosaicism, and Sex Differences in Renal Diseases Barbara R. Migeon McKusick-Nathans Institute of Genetic Medicine, Department of Pediatrics, Johns Hopkins University, Baltimore Maryland ABSTRACT A good deal of sex differences in kidney disease is attributable to sex differences expressed only in the testes, they have to do in the function of genes on the X chromosome. Males are uniquely vulnerable to with testicular function and fertility. With mutations in their single copy of X-linked genes, whereas females are often mosaic, one X chromosome, males have only a sin- having a mixture of cells expressing different sets of X-linked genes. This cellular gle copy of their X-linked genes. mosaicism created by X inactivation in females is most often advantageous, pro- On the other hand, even though fe- tecting carriers of X-linked mutations from the severe clinical manifestations seen males have two copies of these genes, in males. Even subtle differences in expression of many of the 1100 X-linked genes both are not expressed in the same cell. may contribute to sex differences in the clinical expression of renal diseases. Only one X is programmed to work in each diploid somatic cell. All of the other J Am Soc Nephrol 19: 2052–2059, 2008. doi: 10.1681/ASN.2008020198 X chromosomes in the cell become inac- tive during fetal development. Briefly, compensation for X dosage in our spe- Although being female conveys a protec- with normal kidney function. This re- cies is accomplished by a process that en- tive effect on the progression of chronic view addresses the genetic and epigenetic sures only a single X is active in both renal disease, the basis for this sex differ- programs that contribute to the sex dif- sexes.
    [Show full text]
  • Essential Genetics 5
    Essential genetics 5 Disease map on chromosomes 例 Gaucher disease 単一遺伝子病 天使病院 Prader-Willi syndrome 隣接遺伝子症候群，欠失が主因となる疾患 臨床遺伝診療室 外木秀文 Trisomy 13 複数の遺伝子の重複によって起こる疾患 挿画 Koromo 遺伝子の座位あるいは欠失等の範囲を示す Copyright (c) 2010 Social Medical Corporation BOKOI All Rights Reserved. Disease map on chromosome 1 Gaucher disease Chromosome 1q21.1 1p36 deletion syndrome deletion syndrome Adrenoleukodystrophy, neonatal Cardiomyopathy, dilated, 1A Zellweger syndrome Charcot-Marie-Tooth disease Emery-Dreifuss muscular Hypercholesterolemia, familial dystrophy Hutchinson-Gilford progeria Ehlers-Danlos syndrome, type VI Muscular dystrophy, limb-girdle type Congenital disorder of Insensitivity to pain, congenital, glycosylation, type Ic with anhidrosis Diamond-Blackfan anemia 6 Charcot-Marie-Tooth disease Dejerine-Sottas syndrome Marshall syndrome Stickler syndrome, type II Chronic granulomatous disease due to deficiency of NCF-2 Alagille syndrome 2 Copyright (c) 2010 Social Medical Corporation BOKOI All Rights Reserved. Disease map on chromosome 2 Epiphyseal dysplasia, multiple Spondyloepimetaphyseal dysplasia Brachydactyly, type D-E, Noonan syndrome Brachydactyly-syndactyly syndrome Peters anomaly Synpolydactyly, type II and V Parkinson disease, familial Leigh syndrome Seizures, benign familial Multiple pterygium syndrome neonatal-infantile Escobar syndrome Ehlers-Danlos syndrome, Brachydactyly, type A1 type I, III, IV Waardenburg syndrome Rhizomelic chondrodysplasia punctata, type 3 Alport syndrome, autosomal recessive Split-hand/foot malformation Crigler-Najjar
    [Show full text]
  • Inheritest 500 PLUS
    Inheritest® 500 PLUS 525 genes Specimen ID: 00000000010 Container ID: H0651 Control ID: Acct #: LCA-BN Phone: SAMPLE REPORT, F-630049 Patient Details Specimen Details Physician Details DOB: 01/01/1991 Date Collected: 08/05/2019 12:00 (Local) Ordering: Age (yyy/mm/dd): 028/07/04 Date Received: 08/06/2019 Referring: Gender: Female Date Entered: 08/06/2019 ID: Patient ID: 00000000010 Date Reported: 08/21/2019 15:29 (Local) NPI: Ethnicity: Unknown Specimen Type: Blood Lab ID: MNEGA Indication: Carrier screening Genetic Counselor: None SUMMARY: POSITIVE POSITIVE RESULTS DISORDER (GENE) RESULTS INTERPRETATION Spinal muscular atrophy AT RISK AT RISK to be a silent carrier (2+0). For ethnic-specific risk (SMN1) 2 copies of SMN1; positive for revisions see Methods/Limitations. Genetic counseling is NMID: NM_000344 c.*3+80T>G SNP recommended. Risk: AT INCREASED RISK FOR AFFECTED PREGNANCY. See Additional Clinical Information. NEGATIVE RESULTS DISORDER (GENE) RESULTS INTERPRETATION Cystic fibrosis NEGATIVE This result reduces, but does not eliminate the risk to be a (CFTR) carrier. NMID: NM_000492 Risk: NOT at an increased risk for an affected pregnancy. Fragile X syndrome NEGATIVE: Not a carrier of a fragile X expansion. (FMR1) 29 and 36 repeats NMID: NM_002024 Risk: NOT at an increased risk for an affected pregnancy. ALL OTHER DISORDERS NEGATIVE This result reduces, but does not eliminate the risk to be a carrier. Risk: The individual is NOT at an increased risk for having a pregnancy that is affected with one of the disorders covered by this test. For partner's gene-specific risks, visit www.integratedgenetics.com.
    [Show full text]
  • A Model of Autosomal Recessive Alport Syndrome in English Cocker Spaniel Dogs
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Kidney International, Vol. 54 (1998), pp. 706–719 A model of autosomal recessive Alport syndrome in English cocker spaniel dogs GEORGE E. LEES,R.GAYMAN HELMAN,CLIFFORD E. KASHTAN,ALFRED F. MICHAEL,LINDA D. HOMCO, NICHOLAS J. MILLICHAMP,YOSHIFUMI NINOMIYA,YOSHIKAZU SADO,ICHIRO NAITO, and YOUNGKI KIM Texas Veterinary Medical Center, Texas A&M University, College Station, Texas, Oklahoma Animal Disease Diagnostic Laboratory, Oklahoma State University, Stillwater, Oklahoma, and Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, USA; Department of Molecular Biology and Biochemistry, Okayama University Medical School, Okayama, and Divisions of Immunology and Ultrastructural Biology, Shigei Medical Research Institute, Okayama, Japan A model of autosomal recessive Alport syndrome in English cause progressive glomerular disease [1–3]. In humans with cocker spaniel dogs. Alport syndrome (AS), the nephropathy is frequently asso- Background. Dogs with naturally occurring genetic disorders of basement membrane (type IV) collagen may serve as animal ciated with sensorineural hearing loss and ocular abnormal- models of Alport syndrome. ities. Distinctive ultrastructural changes in glomerular base- Methods. An autosomal recessive form of progressive heredi- ment membranes (GBM) of affected individuals is a tary nephritis (HN) was studied in 10 affected, 3 obligate carrier, prominent characteristic of these disorders [1–3]. and 4 unaffected English cocker spaniel (ECS) dogs. Clinical, In humans AS usually is X-linked, resulting from muta- pathological, and ultrastructural features of the disease were a characterized. Expression of basement membrane (BM) proteins tions in the COL4A5 gene, which encodes the 5 chain of was examined with an immunohistochemical technique using type IV collagen [1, 4].
    [Show full text]
  • EUROCAT Syndrome Guide
    JRC - Central Registry european surveillance of congenital anomalies EUROCAT Syndrome Guide Definition and Coding of Syndromes Version July 2017 Revised in 2016 by Ingeborg Barisic, approved by the Coding & Classification Committee in 2017: Ester Garne, Diana Wellesley, David Tucker, Jorieke Bergman and Ingeborg Barisic Revised 2008 by Ingeborg Barisic, Helen Dolk and Ester Garne and discussed and approved by the Coding & Classification Committee 2008: Elisa Calzolari, Diana Wellesley, David Tucker, Ingeborg Barisic, Ester Garne The list of syndromes contained in the previous EUROCAT “Guide to the Coding of Eponyms and Syndromes” (Josephine Weatherall, 1979) was revised by Ingeborg Barisic, Helen Dolk, Ester Garne, Claude Stoll and Diana Wellesley at a meeting in London in November 2003. Approved by the members EUROCAT Coding & Classification Committee 2004: Ingeborg Barisic, Elisa Calzolari, Ester Garne, Annukka Ritvanen, Claude Stoll, Diana Wellesley 1 TABLE OF CONTENTS Introduction and Definitions 6 Coding Notes and Explanation of Guide 10 List of conditions to be coded in the syndrome field 13 List of conditions which should not be coded as syndromes 14 Syndromes – monogenic or unknown etiology Aarskog syndrome 18 Acrocephalopolysyndactyly (all types) 19 Alagille syndrome 20 Alport syndrome 21 Angelman syndrome 22 Aniridia-Wilms tumor syndrome, WAGR 23 Apert syndrome 24 Bardet-Biedl syndrome 25 Beckwith-Wiedemann syndrome (EMG syndrome) 26 Blepharophimosis-ptosis syndrome 28 Branchiootorenal syndrome (Melnick-Fraser syndrome) 29 CHARGE
    [Show full text]
  • Alport Syndrome
    THE VOICE OF THE PATIENT Externally Led Patient–Focused Drug Development Meeting on Alport Syndrome Public Meeting: August 3, 2018 Report Date: November 1, 2019 Submitted as patient experience data for consideration Pursuant to section 569C of the Federal Food, Drug, and Cosmetic Act to: Center for Drug Evaluation and Research (CDER) U.S. Food and Drug Administration (FDA) This report reflects the National Kidney Foundation’s and Alport Syndrome Foundation’s accounts of the perspectives of patients and caregivers who participated in an Externally Led Patient-Focused Drug Development Meeting, an effort to support the FDA’s Patient-Focused Drug Development Initiative © 2019 National Kidney Foundation, Inc National Kidney Foundation 1 Alport Syndrome Foundation VOICE OF THE PATIENT Report on the Externally Led Patient-Focused Drug Development Meeting on Alport Syndrome AUTHORS, COLLABORATORS, REVIEWERS David L. Feldman, PhD, National Kidney Foundation (Author) Ginny Vachon, PhD, Principal Medvantage (Medical writer; author) Clifford E. Kashtan, MD, University of Minnesota Medical School (Honorary chair) Michelle Rheault, MD, University of Minnesota Medical School (Co-chair) James Simon, MD, Cleveland Clinic (Co-chair) Gina Parziale, CFRE, Alport Syndrome Foundation James McCann, BS, National Kidney Foundation (Editor) James Valentine, MHS, JD, Hyman, Phelps, & McNamara (Moderator) Sharon Lagas, Patient and Founder, Alport Syndrome Foundation DISCLOSURES Dr. Kashtan declares the following relationships: Research funding from: Novartis Pharmaceuticals,
    [Show full text]