Espinosa-Parrilla Y, Navarro G, Morell M, Abella E, Estivill X, Sala N
Centre de Genètica Mèdica i Molecular, Institut de Recerca Oncològica, Barcelona, Spain.
Thromb Haemost. 2000 Jan;83(1):102-6.
The multifactorial character of thrombotic disease is shown in a Spanish pedigree in which the propositus, with recurrent deep vein thrombosis, inherited the factor V R/Q506 mutation, the prothrombin 20210G/A variant and type III Protein S deficiency. Among 14 relatives carrying one or two of these three risk factors, thrombosis is present in a heterozygote for R/Q506 and in another for 20210G/A, who also had slightly positive antiphospholipid antibodies. Type I PS deficiency was also found in a young asymptomatic woman. PROS1 analysis showed coexistence of type III and type I PS deficiency to be associated with heterozygosity and homozygosity, respectively, for the P460 or PS Heerlen allele of the S/P460 variant. Analysis of PS values in this and other pedigrees segregating this variant revealed that not only free but also mean total PS levels are slightly but significantly lower in the SP460 heterozygotes than in the SS460 homozygotes. These findings strongly suggest a role of the P460 variant in the expression of the PS deficient phenotype.
在一个西班牙家系中显示了血栓形成疾病的多因素特征，该家系中的先证者患有复发性深静脉血栓形成，遗传了因子V R/Q506突变、凝血酶原20210G/A变异和III型蛋白S缺乏症。在携带这三种危险因素中的一种或两种的14名亲属中，R/Q506杂合子和20210G/A杂合子中存在血栓形成，后者还具有轻度阳性抗磷脂抗体。在一名年轻无症状女性中也发现了I型PS缺乏症。PROS1分析表明，III型和I型PS缺乏症的共存分别与S/P460变体的P460或PS海尔伦等位基因的杂合性和纯合性相关。对这个家系以及其他分离该变体的家系中的PS值进行分析发现，不仅游离PS水平，而且平均总PS水平在SP460杂合子中均略低于但显著低于SS460纯合子。这些发现强烈表明P460变体在PS缺乏表型的表达中起作用。
