Hereditary protein S deficiency leads to ischemic stroke

Wang,Zhao‑Hui; Zhao,Zhi‑Jun; Xu,Kang; Sun,Guo‑Bing; Song,Lin; Yin,Hong‑Xiang; Chen,Xiao‑Qi

doi:10.3892/mmr.2015.3793

Hereditary protein S deficiency leads to ischemic stroke

Authors:
- Zhao‑Hui Wang
- Zhi‑Jun Zhao
- Kang Xu
- Guo‑Bing Sun
- Lin Song
- Hong‑Xiang Yin
- Xiao‑Qi Chen
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Affiliations: Department of Neurology, Hanyang Hospital, Wuhan University of Science and Technology, Wuhan, Hubei 430050. P.R. China, Department of Ultrasonic Diagnosis and Interventional Therapy, The First Hospital Affiliated to Henan University, Kaifeng, Henan 475001, P.R. China, Department of Neurology, Xinhua Hospital of Hubei, Wuhan, Hubei 430015, P.R. China
Published online on: May 18, 2015 https://doi.org/10.3892/mmr.2015.3793
Pages: 3279-3284
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Hereditary protein S (PS) deficiency is an independent risk factor for venous thromboembolism. However, the correlation between PS and arterial thrombotic disease, such as cerebral thrombosis, is not clear. The present study focused on the molecular mechanisms underlying ischemic stroke caused by a PS gene mutation in one family. The activity of antithrombin, protein C and PS in the plasma of the proband was measured, and the genes encoding PS were amplified and sequenced. The cellular localization and expression of PS were analyzed in HEK‑293 cells. The proband was a 50‑year‑old male. Plasma PS activity of the proband was 38.9%, which was significantly decreased compared with normal levels. Sequencing analysis revealed a PROS1 c.1486_1490delGATTA mutation on exon 12. This frameshift mutation converts Asp496 in the precursor PS into the termination codon. In addition, the PROS1 mutation was correlated with low PS activity in the family. Functional tests revealed that the mutant protein aggregated in the cytoplasm and its secretion and expression decreased. In conclusion, protein S mutation appeared to be the primary cause of thrombosis in the family of the present study. However, the correlation between PS deficiency and ischemic stroke requires further investigation.

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