Castoldi E, Lunghi B, Mingozzi F, Muleo G, Redaelli R, Mariani G, Bernardi F
Department of Biochemistry and Molecular Biology, Ferrara University, Italy.
Haematologica. 2001 Jun;86(6):629-33.
Factor V (FV) deficiency is a rare bleeding disorder whose molecular bases are poorly characterized. We have recently described a FV missense mutation (Y1702C) predicting reduced FV levels in a thrombophilic patient and in a healthy individual. The aim of the present work was to assess the prevalence of the FV Y1702C mutation among subjects with FV deficiency.
Carriership of the FV Y1702C mutation was tested in 8 patients with severe FV deficiency (FV:C <8%), in 16 individuals with asymptomatic partial FV deficiency (mean FV:C 38.0%, SD 11.6%) and in 9 patients with pseudo-homozygous APC-resistance (mean FV:C 46.2%, SD 3.6%). An AccI-restriction protocol was employed for rapid mutation screening.
The FV Y1702C mutation was detected in two unrelated patients with unmeasurable FV levels (one being homozygous and the other doubly heterozygous for a still unknown mutation) and in one subject with partial FV deficiency (FV:C 30%). A striking difference in bleeding phenotype was observed between the homozygous patient and her asymptomatic brother with the same FV genotype. A multi-point FV haplotype analysis was performed in all unrelated carriers of the FV Y1702C mutation. Three haplotypes were found to underlie the mutation in different individuals, suggesting that it might have arisen independently more than once.
FV Y1702C is a common cause of FV deficiency in the Italian population and might be a recurrent mutation.
凝血因子V（FV）缺乏是一种罕见的出血性疾病，其分子基础尚未完全明确。我们最近在一名易栓症患者和一名健康个体中发现了一种FV错义突变（Y1702C），该突变可能导致FV水平降低。本研究旨在评估FV缺乏患者中FV Y1702C突变的发生率。
对8例严重FV缺乏患者（FV:C<8%）、16例无症状部分FV缺乏个体（平均FV:C 38.0%，标准差11.6%）和9例假纯合APC抵抗患者（平均FV:C 46.2%，标准差3.6%）进行FV Y1702C突变携带者检测。采用AccI限制性内切酶方法进行快速突变筛查。
在两名FV水平不可测的无关患者（一名为纯合子，另一名为仍未知突变的双杂合子）和一名部分FV缺乏患者（FV:C 30%）中检测到FV Y1702C突变。在具有相同FV基因型的纯合子患者和其无症状兄弟之间观察到明显的出血表型差异。对所有FV Y1702C突变的无关携带者进行了多点FV单倍型分析。发现三种单倍型是不同个体中该突变的基础，表明该突变可能不止一次独立出现。
FV Y1702C是意大利人群中FV缺乏的常见原因，可能是一种复发性突变。
