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Thromb Haemost 2000; 84(01): 112-117
DOI: 10.1055/s-0037-1613977
Commentary
Schattauer GmbH

Homozygous Pro74 → Arg Mutation in the Platelet Glycoprotein Ibβ Gene Associated with Bernard-Soulier Syndrome

Shinji Kunishima
1   From the Japanese Red Cross Aichi Blood Center, Japan
,
Yoshiaki Tomiyama
2   The Department of Internal Medicine and Molecular Science, Japan
,
Shigenori Honda
2   The Department of Internal Medicine and Molecular Science, Japan
,
Mariko Fukunishi
3   The Department of Pediatrics, Osaka University Medical School, Japan
,
Junichi Hara
3   The Department of Pediatrics, Osaka University Medical School, Japan
,
Chikako Inoue
1   From the Japanese Red Cross Aichi Blood Center, Japan
,
Tadashi Kamiya
1   From the Japanese Red Cross Aichi Blood Center, Japan
,
Hidehiko Saito
4   The First Department of Internal Medicine, Nagoya University School of Medicine, Japan
› Author Affiliations
This work was supported in part by The Hibino Memorial Medical Research Fund.
We would like to thank Dr. Jose A Lopez for helpful discussions and critical reading of the manuscript and Dr Kazuo Ozawa for support.
Further Information

Publication History

Received 03 December 1999

Accepted after revision 15 February 2000

Publication Date:
10 December 2017 (online)

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Summary

Bernard-Soulier syndrome (BSS) is an autosomal recessive bleeding disorder due to quantitative or qualitative abnormalities in the glycoprotein (GP) Ib/IX/V complex, the platelet receptor for von Willebrand factor. This complex is composed of four subunits, GPIbα, GPIbβ, GPIX and GPV. We describe here the genetic basis of the disorder in a patient with BSS. Flow cytometric analysis of the patient’s platelets showed greatly reduced GPIbα and GPIX surface expression. Immunoblot analysis disclosed absence of GPIbα, GPIbβ and GPIX in the platelets. DNA sequencing analysis revealed a novel missense mutation in the GPIbβ gene that converts Pro (CCG) to Arg (CGG) at residue 74. Homozygosity of the mutation was confirmed by allele-specific restriction analysis, chromosome 22 microsatellite analysis and quantitative Southern blotting. The mutant GPIbβ was normally transcribed. Transient transfection studies confirmed that mutant GPIbβ impairs surface expression of GPIb/IX, showing that the mutation is responsible for a BSS phenotype observed in the patient.

Keywords

Bernard-Soulier syndrome - chromosome 22 - giant platelets - glycoprotein Ibβ - thrombocytopenia
 

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