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Next-generation sequencing for the diagnosis of MYH9-RD: Predicting pathogenic variants.
Bury, Loredana; Megy, Karyn; Stephens, Jonathan C; Grassi, Luigi; Greene, Daniel; Gleadall, Nick; Althaus, Karina; Allsup, David; Bariana, Tadbir K; Bonduel, Mariana; Butta, Nora V; Collins, Peter; Curry, Nicola; Deevi, Sri V V; Downes, Kate; Duarte, Daniel; Elliott, Kim; Falcinelli, Emanuela; Furie, Bruce; Keeling, David; Lambert, Michele P; Linger, Rachel; Mangles, Sarah; Mapeta, Rutendo; Millar, Carolyn M; Penkett, Christopher; Perry, David J; Stirrups, Kathleen E; Turro, Ernest; Westbury, Sarah K; Wu, John; BioResource, Nihr; Gomez, Keith; Freson, Kathleen; Ouwehand, Willem H; Gresele, Paolo; Simeoni, Ilenia.
Afiliação
  • Bury L; Department of Internal Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy.
  • Megy K; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
  • Stephens JC; NIHR BioResource - Rare Diseases, Cambridge Biomedical Campus, Cambridge University Hospitals, Cambridge, UK.
  • Grassi L; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
  • Greene D; NIHR BioResource - Rare Diseases, Cambridge Biomedical Campus, Cambridge University Hospitals, Cambridge, UK.
  • Gleadall N; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
  • Althaus K; NIHR BioResource - Rare Diseases, Cambridge Biomedical Campus, Cambridge University Hospitals, Cambridge, UK.
  • Allsup D; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
  • Bariana TK; NIHR BioResource - Rare Diseases, Cambridge Biomedical Campus, Cambridge University Hospitals, Cambridge, UK.
  • Bonduel M; Department of Haematology, Addenbrooke's Hospital, Cambridge Biomedical Campus, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
  • Butta NV; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
  • Collins P; NIHR BioResource - Rare Diseases, Cambridge Biomedical Campus, Cambridge University Hospitals, Cambridge, UK.
  • Curry N; Institute for Immunology and Transfusion Medicine, Universitätsmedizin Greifswald Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.
  • Deevi SVV; Transfusion Medicine, Medical Faculty Tübingen, Tübingen, Germany.
  • Downes K; Hull York Medical School, University of Hull, York, UK.
  • Duarte D; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
  • Elliott K; NIHR BioResource - Rare Diseases, Cambridge Biomedical Campus, Cambridge University Hospitals, Cambridge, UK.
  • Falcinelli E; The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free London NHS Foundation Trust, London, UK.
  • Furie B; Hematology/Oncology Department, Hospital de Pediatría "Prof. Dr. Juan P. Garrahan", Buenos Aires, Argentina.
  • Keeling D; Servicio de Hematología y Hemoterapia Hospital, Universitario La Paz-IDIPaz, Madrid, Spain.
  • Lambert MP; Arthur Bloom Haemophilia Centre, Institute of Infection and Immunity, School of Medicine, Cardiff University, UK.
  • Linger R; Department of Clinical Haematology, Oxford Haemophilia and Thrombosis Centre, Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford, UK.
  • Mangles S; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
  • Mapeta R; NIHR BioResource - Rare Diseases, Cambridge Biomedical Campus, Cambridge University Hospitals, Cambridge, UK.
  • Millar CM; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
  • Penkett C; NIHR BioResource - Rare Diseases, Cambridge Biomedical Campus, Cambridge University Hospitals, Cambridge, UK.
  • Perry DJ; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
  • Stirrups KE; NIHR BioResource - Rare Diseases, Cambridge Biomedical Campus, Cambridge University Hospitals, Cambridge, UK.
  • Turro E; Oxford Haemophilia & Thrombosis Centre, Department of Haematology, Oxford University Hospitals NHS Trust, Churchill Hospital, Oxford and the NIHR BRC, Blood Theme, Oxford Centre for Haematology, Oxford, UK.
  • Westbury SK; Department of Internal Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, Perugia, Italy.
  • Wu J; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
  • BioResource N; Churchill Hospital, Oxford University Hospitals, UK.
  • Gomez K; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
  • Freson K; Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
  • Ouwehand WH; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
  • Gresele P; NIHR BioResource - Rare Diseases, Cambridge Biomedical Campus, Cambridge University Hospitals, Cambridge, UK.
  • Simeoni I; Basingstoke and Hampshire Hospital, NHS Foundation Trust, UK.
Hum Mutat ; 41(1): 277-290, 2020 01.
Article em En | MEDLINE | ID: mdl-31562665
ABSTRACT
The heterogeneous manifestations of MYH9-related disorder (MYH9-RD), characterized by macrothrombocytopenia, Döhle-like inclusion bodies in leukocytes, bleeding of variable severity with, in some cases, ear, eye, kidney, and liver involvement, make the diagnosis for these patients still challenging in clinical practice. We collected phenotypic data and analyzed the genetic variants in more than 3,000 patients with a bleeding or platelet disorder. Patients were enrolled in the BRIDGE-BPD and ThromboGenomics Projects and their samples processed by high throughput sequencing (HTS). We identified 50 patients with a rare variant in MYH9. All patients had macrothrombocytes and all except two had thrombocytopenia. Some degree of bleeding diathesis was reported in 41 of the 50 patients. Eleven patients presented hearing impairment, three renal failure and two elevated liver enzymes. Among the 28 rare variants identified in MYH9, 12 were novel. HTS was instrumental in diagnosing 23 patients (46%). Our results confirm the clinical heterogeneity of MYH9-RD and show that, in the presence of an unclassified platelet disorder with macrothrombocytes, MYH9-RD should always be considered. A HTS-based strategy is a reliable method to reach a conclusive diagnosis of MYH9-RD in clinical practice.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Variação Genética / Cadeias Pesadas de Miosina / Predisposição Genética para Doença / Estudos de Associação Genética / Sequenciamento de Nucleotídeos em Larga Escala Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Variação Genética / Cadeias Pesadas de Miosina / Predisposição Genética para Doença / Estudos de Associação Genética / Sequenciamento de Nucleotídeos em Larga Escala Idioma: En Ano de publicação: 2020 Tipo de documento: Article