Rare variants in GP1BB are responsible for autosomal dominant macrothrombocytopenia
| Autor: | Michael Laffan, Nihr BioResource, Anne M. Kelly, Christopher J. Penkett, Daniel P. Hart, Claire Lentaigne, Jonathan Stephens, Paquita Nurden, Eric G. Huizinga, Kate Downes, Ernest Turro, Ilenia Simeoni, Andrew D Mumford, Daniel Greene, David J. Perry, Sofia Papadia, Sarah K Westbury, Willem H. Ouwehand, Kathelijne Peerlinck, R. Campbell Tait, Kathleen Freson, Suthesh Sivapalaratnam, Catherine Roughley, Shinji Kunishima, Kathleen Stirrups, William J. Astle |
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| Přispěvatelé: | Medical Research Council (MRC), Sub Crystal and Structural Chemistry, Crystal and Structural Chemistry |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Gene Expression 030204 cardiovascular system & hematology PHENOTYPE Biochemistry Bernard–Soulier syndrome 0302 clinical medicine Inside BLOOD Commentary 1114 Paediatrics And Reproductive Medicine Medicine Missense mutation Genes Dominant Genetics High-Throughput Nucleotide Sequencing Hematology Phenotype Pedigree GP1BA Platelet Glycoprotein GPIb-IX Complex Female Life Sciences & Biomedicine GLYCOPROTEIN IB-BETA Blood Platelets EXPRESSION Platelet disorder Autosomal dominant macrothrombocytopenia Immunology Hemorrhage PLATELET DISORDERS BERNARD-SOULIER-SYNDROME 1102 Cardiovascular Medicine And Haematology 03 medical and health sciences MISSENSE MUTATION Humans Allele Loss function Alleles GPIB-BETA Science & Technology IX COMPLEX business.industry Genome Human Platelet Count 1103 Clinical Sciences Cell Biology medicine.disease Thrombocytopenia GENE ALPHA 030104 developmental biology Case-Control Studies Mutation business |
| Zdroj: | Blood, 129(4), 520. American Society of Hematology |
| ISSN: | 0006-4971 |
| Popis: | The von Willebrand receptor complex, which is composed of the glycoproteins Ibα, Ibβ, GPV, and GPIX, plays an essential role in the earliest steps in hemostasis. During the last 4 decades, it has become apparent that loss of function of any 1 of 3 of the genes encoding these glycoproteins (namely, GP1BA, GP1BB, and GP9) leads to autosomal recessive macrothrombocytopenia complicated by bleeding. A small number of variants in GP1BA have been reported to cause a milder and dominant form of macrothrombocytopenia, but only 2 tentative reports exist of such a variant in GP1BB. By analyzing data from a collection of more than 1000 genome-sequenced patients with a rare bleeding and/or platelet disorder, we have identified a significant association between rare monoallelic variants in GP1BB and macrothrombocytopenia. To strengthen our findings, we sought further cases in 2 additional collections in the United Kingdom and Japan. Across 18 families exhibiting phenotypes consistent with autosomal dominant inheritance of macrothrombocytopenia, we report on 27 affected cases carrying 1 of 9 rare variants in GP1BB. |
| Databáze: | OpenAIRE |
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