A LARGE DELETION OF THE PROS1 GENE IN A DEEP VEIN THROMBOSIS PATIENT WITH PROTEIN S DEFICIENCY
Abstract number: P-T-458
Yin1 T., Takeshita2 S., Sato1 Y., Sakata3 T., Shin1 Y., Honda1 S., Kawasaki4 T., Tsuji5 H., Kojima6 T., Madoiwa7 S., Sakata7 Y., Murata8 M., Ikeda8 Y., Miyata1 T.
11Research Institute 22Department of Medicine 33Laboratory for Clinical Chemistry, National Cardiovascular Center 44Department of Surgery, Graduate School of Medicine, Osaka University, Osaka 55Division of Blood Transfusion and Cell Therapy, Kyoto Prefectural University of Medicine, Kyoto 66Department of Medical Technology, Nagoya University School of Health Sciences, Nagoya 77Division on Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical School, Shimotsuke, Tochigi 88Department of Medicine, Keio University, Tokyo, Japan
How-to-cite Yin T, Takeshita S, Sato Y, Sakata T, Shin Y, Honda S, Kawasaki T, Tsuji H, Kojima T, Madoiwa S, Sakata Y, Murata M, Ikeda Y, Miyata T. A LARGE DELETION OF THE PROS1 GENE IN A DEEP VEIN THROMBOSIS PATIENT WITH PROTEIN S DEFICIENCY. J Thromb Haemost 2007; 5 Supplement 2: P-T-458
Abstract
Introduction: Protein S (PS) deficiency constitutes an important risk factor of deep vein thrombosis (DVT) and large deletions of PROS1 gene have been verified in some PS deficiency families. The present study investigated whether large deletion in the PROS1 gene could be found as a genetic risk factor for Japanese patients with DVT.
Methods: Multiplex ligation-dependent probe amplification (MLPA) was used to identify deletions in PROS1 in 163 DVT patients. Quantitative PCR (Q-PCR) was applied to validate the deletions. To define the boundary of the deletion, a dense set of SNP and microsatellite markers, covering a 22 Mbp window centered on the PROS1 locus, were analyzed for their allele zygosities. To identify additional genetic variations, all exons of PROS1 were sequenced in the patient with deletion.
Results: One large deletion was identified by MLPA in one DVT patient and validated by Q-PCR. The deletion encompassed the whole PROS1 gene and spanned around 729 kb on chromosome 3. Free PS antigen and PS activity of the patient decreased to 1.2 mg/ml and 10% respectively, while antithrombin, protein C and plasminogen levels were within normal ranges. No other causative mutations were found in PROS1 in this patient. The large deletion in PROS1 was identified in one out of 10 DVT patients (10%) who were characterized with low protein S activity (below 65%) and no possible causative mutations in PROS1.
Conclusions: Large gene deletion in PROS1 could account for DVT with PS deficiency, especially for those without causative mutations in PROS1.
