A large deletion of the PROS1 gene in a deep vein thrombosis patient with protein S deficiency

Tong Yin; Satoshi Takeshita; Yukiko Sato; Toshiyuki Sakata; Yongchol Shin; Shigenori Honda; Tomio Kawasaki; Hajime Tsuji; Tetsuhito Kojima; Seiji Madoiwa; Yoichi Sakata; Mitsuru Murata; Yasuo Ikeda; Toshiyuki Miyata

doi:10.1160/TH07-03-0211

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 98(04): 783-789
DOI: 10.1160/TH07-03-0211

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

A large deletion of the PROS1 gene in a deep vein thrombosis patient with protein S deficiency

Tong Yin

¹Research Institute, National Cardiovascular Center, Osaka, Japan

,

Satoshi Takeshita

²Department of Medicine and National Cardiovascular Center, Osaka, Japan

,

Yukiko Sato

¹Research Institute, National Cardiovascular Center, Osaka, Japan

,

Toshiyuki Sakata

³Laboratory for Clinical Chemistry, National Cardiovascular Center, Osaka, Japan

,

Yongchol Shin

¹Research Institute, National Cardiovascular Center, Osaka, Japan

,

Shigenori Honda

¹Research Institute, National Cardiovascular Center, Osaka, Japan

,

Tomio Kawasaki

⁴Department of Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan

,

Hajime Tsuji

⁵Division of Blood Transfusion and Cell Therapy, Kyoto Prefectural University of Medicine, Kyoto, Japan

,

Tetsuhito Kojima

⁶Department of Medical Technology, Nagoya University of School of Health Sciences, Nagoya, Japan

,

Seiji Madoiwa

⁷Division on Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical School, Shimotsuke, Tochigi, Japan

,

Yoichi Sakata

⁷Division on Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical School, Shimotsuke, Tochigi, Japan

,

Mitsuru Murata

⁸Departments of Laboratory Medicine, Keio University, Tokyo, Japan

,

Yasuo Ikeda

⁹Departments of Internal Medicine, Keio University, Tokyo, Japan

,

Toshiyuki Miyata

¹Research Institute, National Cardiovascular Center, Osaka, Japan

› Author Affiliations

Abstract

Summary

Inherited deficiency of protein S encoded by the PROS1 gene constitutes an important risk factor for deep vein thrombosis (DVT). Nevertheless, although more than 200 deleterious genetic variations in PROS1 have been identified, causative point mutations of PROS1 gene are not detected in approximately half of protein S-deficient families. The present study investigated whether there may exist a large deletion in PROS1 that constitutes a genetic risk factor for Japanese DVT patients. A multiplex ligation-dependent probe amplification analysis was employed to identify the deletions in PROS1 in 163 Japanese patients with DVT. A large gene deletion was identified in one patient who showed 16% protein S activity and did not carry point mutations in PROS1 by DNA sequencing and it was validated by the quantitative PCR method. The deletion spanned at least the whole PROS1 gene (107 kb) and at most from the centromere located downstream of PROS1, to before the D3S3619 marker, the first heterozygous marker in the upstream of PROS1 in chromosome 3. In conclusion, a large deletion in PROS1 was shown to partly account for DVT with protein S deficiency. Screening for large deletions in PROS1 might be warranted in PROS1 causative point mutation-negative DVT patients with protein S deficiency.

Keywords

Gene deletion - deep vein thrombosis - protein S deficiency - PROS1 - MLPA

Full Text

References

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