Morboeuf O, Aiach M, Gandrille S
INSERM Unité 428, UFR des Sciences Pharmaceutiques et Biologiques, Paris, France.
Br J Haematol. 1998 Apr;101(1):10-5. doi: 10.1046/j.1365-2141.1998.00646.x.
Type III protein S (PS) deficiency, characterized by low levels of free PS and normal total PS levels, is often associated with the Ser 460 to Pro substitution. However, some patients bearing this mutation have normal PS levels, suggesting that another gene defect may account for this phenotype. We postulated that this defect was located in the C4b-BP beta-chain gene (C4BPB) and searched for a mutation in the coding regions of this gene in 35 propositi with type III PS deficiency and bearing the Ser 460 to Pro mutation. No mutations explaining the phenotype of type III PS deficiency were identified. We did, however, find two frequent nucleotide changes, one being located in the donor splice site of intron d and the second in the codon corresponding to Asn 137. We used these two polymorphisms to establish C4BPB gene haplotype in five informative type III PS-deficient families and exclude a role of the C4BPB gene in this phenotype of three of them. Finally, increased C4b-BP beta-chain levels were not responsible for the phenotype of type III PS deficiency as the C4BPB haplotype did not correlate with C4b-BP beta-chain levels.
III型蛋白S（PS）缺乏症的特征是游离PS水平低而总PS水平正常，常与Ser 460到Pro的替换相关。然而，一些携带此突变的患者PS水平正常，这表明另一种基因缺陷可能导致了这种表型。我们推测这种缺陷位于C4b - BPβ链基因（C4BPB）中，并在35名患有III型PS缺乏症且携带Ser 460到Pro突变的先证者中搜索该基因编码区的突变。未发现能解释III型PS缺乏症表型的突变。然而，我们确实发现了两个常见的核苷酸变化，一个位于内含子d的供体剪接位点，另一个位于对应于Asn 137的密码子中。我们利用这两个多态性在五个信息丰富的III型PS缺乏症家族中建立C4BPB基因单倍型，并排除了其中三个家族中C4BPB基因在这种表型中的作用。最后，由于C4BPB单倍型与C4b - BPβ链水平不相关，C4b - BPβ链水平升高并非III型PS缺乏症表型的原因。
