Novel heterozygous missense mutation in the second leucine rich repeat of GPIbalpha affects GPIb/IX/V expression and results in macrothrombocytopenia in a patient initially misdiagnosed with idiopathic thrombocytopenic purpura

European Journal of Haematology
Shinji KunishimaH Saito

Abstract

Recent studies have shown that heterozygous carriers of the bleeding disorder Bernard-Soulier syndrome are occasionally identified as isolated case of giant platelet disorder/macrothrombocytopenia or misdiagnosed with idiopathic thrombocytopenic purpura (ITP). We describe here a patient with congenital macrothrombocytopenia who had been diagnosed with ITP. On peripheral blood smears, platelet diameter was approximately 30% larger than normal controls. In the patient's platelets, the expression level of the GPIbIX complex was slightly decreased (70-80% of normal control). Densitometric analysis of immunoblots showed GPIbalpha to be approximately 52% of normal. DNA sequencing analysis revealed a novel heterozygous missense mutation in the GPIbalpha gene that converts Tyr to Asp at residue 54 (Y54D) in the second leucine-rich repeat. Mutant GPIbalpha protein was not detected in the patient's platelets. Transient transfection studies demonstrated that mutant GPIbalpha affects complex expression. These findings suggest that null expression of the mutant GPIbalpha causes decreased density of the complex and results in macrothrombocytopenia.

References

May 25, 1991·Nucleic Acids Research·Y ImaiM Terada
Sep 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·M J HickeyG J Roth
Aug 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·J A LopezG J Roth
Apr 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·J A LopezG J Roth
Sep 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·M J HickeyG J Roth
Dec 5, 2002·International Journal of Hematology·Shinji KunishimaHidehiko Saito
Jan 21, 2003·Laboratory Investigation; a Journal of Technical Methods and Pathology·Shinji KunishimaHidehiko Saito
Oct 22, 2004·Seminars in Thrombosis and Hemostasis·Carlo L Balduini, Anna Savoia
Aug 17, 2005·Journal of Thrombosis and Haemostasis : JTH·A T Nurden
Sep 20, 2005·Blood Reviews·Shinji Kunishima, Hidehiko Saito
Oct 4, 2005·Pediatric Blood & Cancer·Paul S Gaynon
Apr 22, 2006·Acta Crystallographica. Section D, Biological Crystallography·Michihiro Sugahara, Naoki Kunishima

❮ Previous
Next ❯

Citations

Aug 14, 2012·Human Genetics·Carlo L Balduini, Anna Savoia
Nov 26, 2010·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Riki OkitaKingo Fujimura
Nov 18, 2006·Orphanet Journal of Rare Diseases·François Lanza
Dec 1, 2015·La Revue de médecine interne·V Baccini, M C Alessi
Apr 30, 2015·Clinical Genetics·A Pecci
Nov 6, 2014·American Journal of Hematology·Gudrun BragadottirPall T Onundarson
Dec 20, 2013·Hämostaseologie·M GothwalB Zieger
Mar 21, 2013·Journal of Thrombosis and Haemostasis : JTH·C L BalduiniM Seri
Oct 2, 2012·Platelets·Gianmarco PoddaMarco Cattaneo
May 19, 2009·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Chihaya ImaiMakoto Uchiyama
Feb 22, 2012·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Rami A MahfouzSamar Muwakkit
Jun 18, 2014·Human Mutation·Anna SavoiaFrancois Lanza
Sep 30, 2017·Platelets·Maha Othman, Jonas Emsley
Dec 4, 2019·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Zeynep C ÖzdemirÖzcan Bör
Aug 2, 2021·Journal of Thrombosis and Haemostasis : JTH·Eva LeinøeMaria Rossing

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.