A large deletion of the PROS1 gene in a deep vein thrombosis patient with protein S deficiency
A large deletion of the PROS1 gene in a deep vein thrombosis patient with protein S deficiency
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DOI：
10.1160/th07-03-0211
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发表时间：
2007-10
影响因子：
6.7
通讯作者：
T. Yin;S. Takeshita;Yukiko Sato;T. Sakata;Yongchol Shin;S. Honda;T. Kawasaki;H. Tsuji;T. Kojima;S. Madoiwa;Y. Sakata;M. Murata;Y. Ikeda;T. Miyata
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文献类型：
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作者：
T. Yin;S. Takeshita;Yukiko Sato;T. Sakata;Yongchol Shin;S. Honda;T. Kawasaki;H. Tsuji;T. Kojima;S. Madoiwa;Y. Sakata;M. Murata;Y. Ikeda;T. Miyata
摘要由PrOS1基因编码的S蛋白的遗传性缺陷是深静脉血栓形成的重要危险因素。然而，尽管已经鉴定出200多种有害的基因变异，但在大约一半的S蛋白缺乏家系中没有检测到PROS1基因的致病点突变。这项研究调查了PROS1是否可能存在大的缺失，这构成了日本DVT患者的遗传风险因素。采用多重连接依赖的探针扩增分析方法对163例日本DVT患者进行PROS1基因缺失分析。1例S蛋白活性为16%的患者经测序证实存在较大的基因缺失，未发现PROS1点突变，经定量聚合酶链式反应证实。该缺失至少覆盖了整个PROS_1基因(107kb)，最多从位于PRO_1下游的着丝粒到D3S3619标记之前，D3S3619标记是位于PRO_1上游的第一个杂合性标记。在蛋白S缺乏的PROS1点突变阴性的DVT患者中，可能有必要进行PROS1大片段缺失的筛查。
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.