Homozygous Type I Protein C Deficiency in Two Unrelated Families Exhibiting Thrombophilia Related to Ala136→Pro or Arg286→His Mutations-猫眼课题宝

两个不相关家族的纯合 I 型蛋白 C 缺乏症，表现出与 Ala136→Pro 或 Arg286→His 突变相关的血栓形成倾向

DOI：

发表时间：

1994

期刊：

Thrombosis and Haemostasis

影响因子：

6.7

通讯作者：

中科院分区：

医学2区

文献类型：

作者：

G. Long;J. Tomczak;I. Rainville;M. Dreyfus;W. Schramm;H. Schwarz

摘要：在两个不相关的纯合子I型蛋白C缺乏症患者中发现了单独的单核苷酸突变。每个突变最初是通过聚合酶链式反应扩增产物的直接DNA测序建立的，导致氨基酸替换。第一个突变(PCClamart)导致蛋白质的第二个表皮生长因子样域的Ala136到Pro的替换。第二个突变(PCMtinchen)导致Arg286取代丝氨酸蛋白酶结构域。比较这两个突变的位置和两个区域在同源维生素K依赖的血浆蛋白中的相对保守性，与两个人蛋白C缺乏和疾病的严重程度的差异是一致的。这两种突变都会导致自然产生的限制性内切酶位点的取消，从而允许对突变进行独立确认，并对家庭成员中的蛋白C缺乏症进行快速和明确的基因分析。在这两个家族中，基因分析在基于临床实验室测量的蛋白C状态分配不明确或不正确的情况下被证明是有用的。

Summary Separate single nucleotide mutations have been identified in two unrelated homozygous type I protein C deficient individuals suffering from thrombophilia. Each mutation, initially established by direct DNA sequencing of polymerase chain reaction amplification products, results in an amino acid substitution. The first mutation (PCClamart) results in an Ala136 to Pro substitution in the protein’s second epidermal growth factor-like domain. The second mutation (PCMtinchen) results in an Arg286 to His substitution in the serine protease domain. Comparison of the location of these two mutations and the relative conservation of the two regions in homologous vitamin K-dependent plasma proteins is consistent with the difference in severity of protein C deficiency and disease in the two individuals. Both mutations result in the abolition of a naturally occurring restriction endonuclease site, thereby allowing independent confirmation of the mutations and rapid and unambiguous genetic analysis of protein C deficiency in family members. In both families, the genetic analysis has proven useful in cases where an assignment of the protein C status based upon clinical laboratory measurements was either ambiguous or incorrect.