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Thromb Haemost 2000; 84(04): 675-679
DOI: 10.1055/s-0037-1614086
Review Article
Schattauer GmbH

Histidine-rich Glycoprotein (HRG) Tokushima 2: Novel HRG Deficiency, Molecular and Cellular Characterization

Toshio Shigekiyo
1   From the First Department of Internal Medicine, School of Medicine, The University of Tokushima, Tokushima
,
Hidemasa Yoshida
3   Department of Life Science, Faculty of Science, Himeji Institute of Technology, Hyogo, Japan
,
Yasuhiko Kanagawa
1   From the First Department of Internal Medicine, School of Medicine, The University of Tokushima, Tokushima
,
Koichi Satoh
2   Department of Neurological Surgery, School of Medicine, The University of Tokushima, Tokushima
,
Sadao Wakabayashi
3   Department of Life Science, Faculty of Science, Himeji Institute of Technology, Hyogo, Japan
,
Toshio Matsumoto
1   From the First Department of Internal Medicine, School of Medicine, The University of Tokushima, Tokushima
,
Takehiko Koide
3   Department of Life Science, Faculty of Science, Himeji Institute of Technology, Hyogo, Japan
› Author AffiliationsThis study was supported in part by a Grant-in-Aid for Scientific Research (no. 09671116) to T. S. and a Grant-in-Aid for Scientific Research on a Priority Area (Intracellular Proteolysis) to T. K. from the Minister of Education, Science, Sports, and Culture of Japan.
The authors are grateful to Dr. Don Foster for supplying ZMB3 expression vector.
Further Information

Publication History

Received 13 January 2000

Accepted 20 April 2000

Publication Date:
11 December 2017 (online)

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Summary

The proband, a 76-year-old woman, suffered from dural arteriovenous fistula. Her plasma histidine-rich glycoprotein (HRG) level was 50% of the normal level. A low level of plasma HRG was also found in her third daughter. A single nucleotide substitution of T to C was found at nucleotide position 11,438 in exon 6 of the HRG gene from the proband, converting Cys223 to Arg in the second cystatin-like domain. The same mutation was also identified in her third daughter, but not in the other four family members having normal HRG levels or in 50 unrelated healthy Japanese individuals. Expression studies in BHK cells showed that substantial intracellular degradation of the mutant occurred and only about 40% of the recombinant HRG mutant was secreted. These results indicate that congenital HRG deficiency caused by a substitution of Cys223 to Arg is hereditary in this family.

Key words

Congenital histidine-rich glycoprotein deficiency - histidine-rich glycoprotein - thrombosis
 

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