Characterisation of patients with Glanzmann thrombasthenia and identification of 17 novel mutations

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Issue: 2015: 113/4 (Apr) pp. 671–909
Pages: 782-791
Ahead of Print: 2014-11-06

Characterisation of patients with Glanzmann thrombasthenia and identification of 17 novel mutations

K. Sandrock-Lang (1), J. Oldenburg (2), V. Wiegering (3), S. Halimeh (4), S. Santoso (5), K. Kurnik (6), L. Fischer (7), D. A. Tsakiris (8), M. Sigl-Kraetzig (9), B. Brand (10), M. Bührlen (11), K. Kraetzer (1), N. Deeg (1), M. Hund (1), E. Busse (1), A. Kahle (1), B. Zieger (1)

(1) Department of Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg, Germany; (2) Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany; (3) Department of Pediatric Hematology, Oncology and Neurooncology, University Children’s Hospital Würzburg, Germany; (4) Coagulation Centre Rhine Ruhr, Duisburg, Germany; (5) Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University of Giessen, Germany; (6) Dr. von Hauner’s Children’s Hospital, Paediatric Haemophilia Centre, Munich, Germany; (7) Division of Pediatric Oncology, University Hospital of Leipzig, Leipzig, Germany; (8) Department of Haematology, University Hospital Basel, Basel, Switzerland; (9) Practice for pediatrics with haemophilia treatment center, Blaubeuren and IPFW Blaubeuren – München, Munich, Germany; (10) Division of Hematology, University Hospital, Zurich, Switzerland; (11) Center for Thrombosis and Hemostasis, Professor-Hess-Kinderklinik, Klinikum Bremen-Mitte, Bremen, Germany


Glanzmann thrombasthenia, platelet function defect, glycoprotein αIIbβ3


Glanzmann thrombasthenia (GT) is an autosomal recessive bleeding disorder characterised by quantitative and/or qualitative defects of the platelet glycoprotein (GP) IIb/IIIa complex, also called integrin αIIbβ3. αIIbβ3 is well known as a platelet fibrinogen receptor and mediates platelet aggregation, firm adhesion, and spreading. This study describes the molecular genetic analyses of 19 patients with GT who were diagnosed on the basis of clinical parameters and platelet analyses. The patients’ bleeding signs include epistaxis, mucocutaneous bleeding, haematomas, petechiae, gastrointestinal bleeding, and menorrhagia. Homozygous or compound heterozygous mutations in ITGA2B or ITGB3 were identified as causing GT by sequencing of genomic DNA. All exons including exon/intron boundaries of both genes were analysed. In a patient with an intronic mutation, splicing of mRNA was analysed using reverse transcriptase (RT)-PCR of platelet-derived RNA. In short, 16 of 19 patients revealed 27 different mutations (ITGA2B: n=17, ITGB3: n=10). Seventeen of these mutations have not been published to date. Mutations in ITGA2B or ITGB3 were identified as causing GT in 16 patients. We detected a total of 27 mutations in ITGA2B and ITGB3 including 17 novel missense, nonsense, frameshift and splice site mutations. In addition, three patients revealed no molecular genetic anomalies in ITGA2B or ITGB3 that could explain the suspected diagnosis of GT. We assume that these patients may harbour defects in a regulatory element affecting the transcription of these genes, or other proteins may exist that are important for activating the αIIbβ3 complex that may be affected.

You may also be interested in...

Ronit Mor-Cohen1*, Nurit Rosenberg1*, Hava Peretz 2, Meytal Landau 1,3, Barry S. Coller 4, Abdalla Awidi 5, Uri Seligsohn1

Thromb Haemost 2007 98 6: 1257-1265


Online Supplementary Material

S. Loroch (1), K. Trabold (2), S. Gambaryan (2, 3), C. Reiß (2), K. Schwierczek (2), I. Fleming (4, 5), A. Sickmann (1, 6, 7), W. Behnisch (8), B. Zieger (9), R. P. Zahedi (1), U. Walter (2, 5), K. Jurk (2, 5)

Thromb Haemost 2017 117 3: 556-569


Online Supplementary Material

G. Mao (1), J. Jin (1, 2), S. P. Kunapuli (1, 2), A. K. Rao (1, 3)

Thromb Haemost 2016 116 5: 931-940