Thromb Haemost 2004; 92(05): 1040-1051
DOI: 10.1160/TH04-03-0170
Platelets and Blood Cells
Schattauer GmbH

Glanzmann thrombasthenia Frankfurt I is associated with a point mutation Thr176Ile in the N-terminal region of αIIb subunit integrin

Dagmar Westrup
1   Deutsche Klinik für Diagnostik, Wiesbaden, Germany
,
Sentot Santoso
2   Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany
,
Katja Follert-Hagendorff
1   Deutsche Klinik für Diagnostik, Wiesbaden, Germany
,
Steffen Bassus
1   Deutsche Klinik für Diagnostik, Wiesbaden, Germany
,
Melitta Just
3   Aventis, Frankfurt-Hoechst, Germany
,
Bernd Jablonka
3   Aventis, Frankfurt-Hoechst, Germany
,
Carl M. Kirchmaier
1   Deutsche Klinik für Diagnostik, Wiesbaden, Germany
› Institutsangaben

Financial support: This work has been supported, in part, by a grant from the Deutsche Forschungsgemeinschaft, Bonn (DFG Ki 1-1 and SFB547 (SS)).
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Publikationsverlauf

Received 18. März 2004

Accepted after revision 25. August 2004

Publikationsdatum:
04. Dezember 2017 (online)

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Summary

In this study, we report on the characterization of a patient with Glanzmann thrombasthenia (GT). Immunochemical analysis on platelets from the patient showed that the expression of αIIbβ3 was only 25% of that in normal healthy controls, suggesting a case of GT. Functional analysis revealed a total lack of fibrinogen binding capacity. Molecular genetic analysis of the full-length cDNA sequences of αIIb and β3 subunits showed a novel point mutation C621T in αIIb cDNA, leading to a missense substitution of threonine for isoleucine at position 176. Coexpression of normal β3 and mutant αIIbI176 isoform in mammalian cells showed a marked reduction in the expression of αIIbβ3 heterodimer when compared to the wild-type and a decreased intracellular level of αIIb. The T176 I mutation is located in the N-terminal region in the W3:1-2 connecting strand of the β-propeller. These data suggest that the N-terminal αIIb domain plays an important structural role in the formation of heterodimer and that it is also involved in fibrinogen binding.