%0 Journal Article
%T Venous thromboembolic risk and protein S deficiency: ethnic difference and remaining issues<br>
%A Tong Yin
%A Toshiyuki Miyata
%A <br>
%J 老年心脏病学杂志(英文版)
%D 2009
%I Science Press
%X Protein S deficiency is an autosomal dominant disorder that results from mutations in the protein S gene (PROS1). Inherited deficiency of protein S constitutes a risk factor for venous thromboembolism. Protein S functions as a nonenzymatic cofactor for activated protein C in the proteolytic degradation of coagulation factors V a and Villa. The frequency of protein S deficiency seems to differ between populations. More than 200 rare mutations in PROS1 have been identified in patients with protein S deficiency. Among the prevalent mutations within PROS1, the S460P substitution (known as Heerlen polymorphism) detected in Caucasians and the K196E substitution (known as protein S Tokushima) found in Japanese have been intensively studied for their structures and potential functions in the disorder of protein S deficiency. Until now, causative mutations in PROS1 have been found in only approximately 50% of cases with protein S deficiency. Co-segregation analysis of microsatellite haplotypes with protein S deficiency in families with protein S deficiency suggests that the causative defects in the PROS1 mutation-negative patients are located in or close to the PROS 1 gene. Large PROS 1 gene deletions have been identified in 3 out of 9 PROS 1 mutation-negative Swedish VTE families with protein S deficiency and 1 out of 6 PROS1 mutation-negative Japanese patients with protein S deficiency. Intensive sequencing of the entire PROS 1 gene, including introns, may be needed to identify the cryptic mutations in those patients, and these efforts might uncover the pathogenesis of protein S deficiency.
%K protein S deficiency
%K PROS 1
%K thrombophilia
%K mutation
%K genetic defects<br>
%U http://www.alljournals.cn/get_abstract_url.aspx?pcid=A9DB1C13C87CE289EA38239A9433C9DC&cid=AD36F34DDC3BA7B0&jid=4DC702B3A2386A4814E2FF9CFB799B27&aid=34A3F32A9B1C6625B190A3043A289082&yid=DE12191FBD62783C&vid=B31275AF3241DB2D&iid=CA4FD0336C81A37A&sid=708DD6B15D2464E8&eid=2A8D03AD8076A2E3&journal_id=1671-5411&journal_name=Journalofgeriatriccardiology:JGC&referenced_num=0&reference_num=67