Heterogenous Expression of Glycoprotein lb, IX and V in Platelets from Two Patients with Bernard-Soulier Syndrome Caused by Different Genetic Abnormalities

Masaaki Noda; Kingo Fujimura; Toshiro Takafuta; Takeshi Shimomura; Tetsuro Fujlmoto; Naomasa Yamamoto; Kenjiro Tanoue; Morio Arai; Akira Suehiro; Eizo Kakishita; Akemi Shimasaki; Atsushi Kuramoto

doi:10.1055/s-0038-1649956

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1995; 74(06): 1411-1415
DOI: 10.1055/s-0038-1649956

Original Articles

Clinical Studies

Schattauer GmbH Stuttgart

Heterogenous Expression of Glycoprotein lb, IX and V in Platelets from Two Patients with Bernard-Soulier Syndrome Caused by Different Genetic Abnormalities

Masaaki Noda

¹The Department of Hematology and Oncology, Division of Clinical Research, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

,

Kingo Fujimura

¹The Department of Hematology and Oncology, Division of Clinical Research, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

,

Toshiro Takafuta

¹The Department of Hematology and Oncology, Division of Clinical Research, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

,

Takeshi Shimomura

¹The Department of Hematology and Oncology, Division of Clinical Research, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

,

Tetsuro Fujlmoto

¹The Department of Hematology and Oncology, Division of Clinical Research, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

,

Naomasa Yamamoto

³The Department of Cardiovascular Research, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

,

Kenjiro Tanoue

³The Department of Cardiovascular Research, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

,

Morio Arai

²The Department of Clinical Pathology, Tokyo Medical College, Tokyo, Japan

,

Akira Suehiro

⁴The Department of Second Internal Medicine, Hyogo College of Medicine, Hyogo, Japan

,

Eizo Kakishita

⁴The Department of Second Internal Medicine, Hyogo College of Medicine, Hyogo, Japan

,

Akemi Shimasaki

⁵The Department of Internal Medicine, Himeji National Hospital, Hyogo, Japan

,

Atsushi Kuramoto

¹The Department of Hematology and Oncology, Division of Clinical Research, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

› Author Affiliations

Abstract

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Summary

Bernard-Soulier syndrome (BSS) is a rare inherited bleeding disorder, which is caused by deficiency or decrease of the platelet GPIb/IX/V complex. Analysis of two patients with BSS by How cytometry of the blood revealed different expression patterns of the components of the GPIb/IX/V complex. In case 1, GPIX was completely absent but residual amounts of GPIbα and GPV were detectable; in case 2, GPIbα was completely absent. We amplified the coding regions of GPIbα, GPIbß, GPV, and GPIX from the patients’ genomic DNA with the polymerase chain reaction (PCR) and sequenced the PCR products. In case 1, we identified a point mutation in the GPIX coding region that changes the codon for tryptophan-126 (TGG) to a nonsense codon (TGA). In case 2, we found a deletion of nucleotide within seven adenine repeats at the position of 1932 to 1938 in the coding region of GPIbα, which causes a frame shift that results in 58 altered amino acids and a premature stop codon. These genetic changes alter the transmembrane domain of GPIX or GPIbα and, therefore, would prevent proper insertion of the proteins in the plasma membrane. Thus, abnormality of a single component protein (GPIX or GPIbα) alters the assembly of the GPIb/IX/V complex and causes heterogenous surface expression of GPIbα, GPV and GPIX.

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References

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