Sugahara Y, Miura O, Hirosawa S, Aoki N
First Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Thromb Haemost. 1994 Dec;72(6):814-8.
The protein C gene in a patient apparently homozygous for protein C deficiency was analyzed. Two different point mutations, each located in a different allele, were detected to reveal that the patient is a compound heterozygote. Mutation of Arg-178 (CGG) to Gln (CAG) [mutation I] was detected in exon VII, in the vicinity of activation peptide cleavage site by thrombin. Mutation of Cys-331 (TGC) to Arg (CGC) [mutation II] was found in exon IX, at one of the sites involved in disulfide bond formation in the catalytic domain of the heavy chain. The alteration of Cys-331 to Arg disables the formation of the disulfide bond and would alter the protein conformation. Transient expression assays using COS-7 cells transfected with protein C expression vectors containing each one of these two mutations suggested that each of the two mutations would lead to the protein C deficiency by an impairment of secretion of the respective mutant proteins.
对一名明显为蛋白C缺乏纯合子的患者的蛋白C基因进行了分析。检测到两个不同的点突变，每个突变位于不同的等位基因上，结果显示该患者为复合杂合子。在凝血酶激活肽切割位点附近的外显子VII中检测到Arg-178（CGG）突变为Gln（CAG）[突变I]。在重链催化结构域中参与二硫键形成的位点之一的外显子IX中发现了Cys-331（TGC）突变为Arg（CGC）[突变II]。Cys-331突变为Arg会导致二硫键无法形成，并会改变蛋白质构象。使用转染了含有这两种突变之一的蛋白C表达载体的COS-7细胞进行的瞬时表达分析表明，这两种突变中的每一种都会通过损害各自突变蛋白的分泌而导致蛋白C缺乏。
