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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Clericuzio, Carol L. Stewart, Helen Hall, Judith G. Shendure, Jay Scott, Richard H. Buckingham, Kati J. Stumpel, Constance Everman, David B. Fryer, Alan Williams, Marc S. Carey, John C. Curry, Cynthia J. Giovannucci Uzielli, Maria Luisa Irani, Sarosh Sherr, Elliott Whiteford, Margo Hecht, Jacqueline T. Seaver, Laurie H. Krapels, Ingrid P. C. Shively, Kathryn M. Chong, Jessica X. Aylsworth, Arthur S. Devriendt, Koenraad Crow, Yanick J. Graham, John M. Temel, Sehime G. Tabor, Holly K. Bamshad, Michael J. Leroy, Jules G. Nickerson, Deborah A. Bitoun, Pierre Plant, Gordon T. McMillin, Margaret J. Aracena, Mariana I. Robertson, Stephen P. Smith, Joshua D. Weaver, David D. Heidenreich, Randall A. Beck, Anita E. Gildersleeve, Heidi I. S. Mowat, David Splitt, Miranda Gibson, Kate Schorry, Elizabeth K. Hurst, Jane A. |
| Organization | University of Washington Center for Mendelian Genomics |
| Description | Country affiliation: United States Author Affiliation: McMillin MJ ( Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.); Beck AE ( Department of Pediatrics, University of Washington, Seattle, WA 98195, USA); Chong JX ( Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.); Shively KM ( Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.); Buckingham KJ ( Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.); Gildersleeve HI ( Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.); Aracena MI ( Genetic Unit, Hospital Dr. Luis Calvo Mackenna, Santiago 7500539, Chile); Aylsworth AS ( Departments of Pediatrics and Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.); Bitoun P ( Service de Pédiatrie, Hôpital Jean Verdier, Assistance Publique - Hôpitaux de Paris, Bondy 93143, France.); Carey JC ( Department of Pediatrics, University of Utah, Salt Lake City, UT 84108, USA.); Clericuzio CL ( Department of Pediatrics, University of New Mexico, Albuquerque, NM 87131, USA.); Crow YJ ( Manchester Academic Health Science Centre and University of Manchester, Manchester M13 9NT, UK.); Curry CJ ( Genetic Medicine Central California, University of California, San Francisco, Fresno, CA 93701, USA.); Devriendt K ( Centre for Human Genetics, University Hospitals KU Leuven, 3000 Leuven, Belgium.); Everman DB ( Greenwood Genetic Center, Greenwood, SC 29646, USA.); Fryer A ( Department of Clinical Genetics, Alder Hey Children's Hospital, Liverpool L12 2AP, UK.); Gibson K ( Genetic Health Service New Zealand, Christchurch Hospital, Christchurch 8140, New Zealand.); Giovannucci Uzielli ML ( Genetics and Molecular Medicine, Dipartimento di Scieze della Salute, University of Florence, Florence 50132, Italy.); Graham JM ( Division of Clinical Genetics and Dysmorphology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.); Hall JG ( Departments of Medical Genetics and Pediatrics, University of British Columbia and BC Children's Hospital, Vancouver, BC V6H 3N1, Canada.); Hecht JT ( Department of Pediatrics, University of Texas Medical School, Houston, TX 77030, USA.); Heidenreich RA ( Department of Pediatrics, University of New Mexico, Albuquerque, NM 87131, USA.); Hurst JA ( North East Thames Regional Genetic Service, Great Ormond Street Hospital, London WC1N 3BH, UK.); Irani S ( Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UK.); Krapels IP ( Department of Clinical Genetics, School for Oncology and Developmental Biology, Maastricht UMC+, Maastricht 6229 GR, the Netherlands.); Leroy JG ( Princess Elisabeth Children's Hospital, Ghent University Hospital, 9000 Ghent, Belgium.); Mowat D ( Department of Medical Genetics, Sydney Children's Hospital, Sydney, NSW 2031, Australia); Plant GT ( National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK.); Robertson SP ( Department of Women's and Children's Health, University of Otago, Dunedin 9054, New Zealand.); Schorry EK ( Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.); Scott RH ( North East Thames Regional Genetic Service, Great Ormond Street Hospital, London WC1N 3BH, UK.); Seaver LH ( Department of Pediatrics, University of Hawai'i John A. Burns School of Medicine, Honolulu, HI 96826, USA.); Sherr E ( Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA.); Splitt M ( Northern Genetics Service, Institute of Genetic Medicine, Newcastle upon Tyne NE1 3BZ, UK.); Stewart H ( Department of Clinical Genetics, Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford OX3 7LJ, UK.); Stumpel C ( Department of Clinical Genetics, School for Oncology and Developmental Biology, Maastricht UMC+, Maastricht 6229 GR, the Netherlands.); Temel SG ( Department of Medical Genetics, Faculty of Medicine, Uludag University, Bursa 16059, Turkey); Weaver DD ( Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.); Whiteford M ( Department of Clinical Genetics, Southern General Hospital, Glasgow G51 4TF, UK.); Williams MS ( Genomic Medicine Institute, Geisinger Health System, Danville, PA 17822, USA.); Tabor HK ( Division of Genetic Medicine, Seattle Children's Hospital, Seattle, WA 98105, USA); Smith JD ( Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.); Shendure J ( Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.); Nickerson DA ( Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.); Bamshad MJ ( Department of Pediatrics, University of Washington, Seattle, WA 98195, USA) |
| Abstract | Gordon syndrome (GS), or distal arthrogryposis type 3, is a rare, autosomal-dominant disorder characterized by cleft palate and congenital contractures of the hands and feet. Exome sequencing of five GS-affected families identified mutations in piezo-type mechanosensitive ion channel component 2 (PIEZO2) in each family. Sanger sequencing revealed PIEZO2 mutations in five of seven additional families studied (for a total of 10/12 [83%] individuals), and nine families had an identical c.8057G>A (p.Arg2686His) mutation. The phenotype of GS overlaps with distal arthrogryposis type 5 (DA5) and Marden-Walker syndrome (MWS). Using molecular inversion probes for targeted sequencing to screen PIEZO2, we found mutations in 24/29 (82%) DA5-affected families and one of two MWS-affected families. The presence of cleft palate was significantly associated with c.8057G>A (Fisher's exact test, adjusted p value < 0.0001). Collectively, although GS, DA5, and MWS have traditionally been considered separate disorders, our findings indicate that they are etiologically related and perhaps represent variable expressivity of the same condition. |
| ISSN | 00029297 |
| e-ISSN | 15376605 |
| DOI | 10.1016/j.ajhg.2014.03.015 |
| Journal | The American Journal of Human Genetics |
| Issue Number | 5 |
| Volume Number | 94 |
| Language | English |
| Publisher | Cell Press (on behalf of American Society of Human Genetics) |
| Publisher Date | 2014-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Abnormalities, Multiple Genetics Arachnodactyly Arthrogryposis Blepharophimosis Cleft Palate Clubfoot Connective Tissue Diseases Contracture Hand Deformities, Congenital Ion Channels Ophthalmoplegia Retinal Diseases Pathology Child, Preschool Exome Mutation Pedigree Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Human Genetics |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Genetics (clinical) |
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