Poort S R, Michiels J J, Reitsma P H, Bertina R M
Department of Hematology, University Hospital Leiden, The Netherlands.
Thromb Haemost. 1994 Dec;72(6):819-24.
A patient with a severe bleeding tendency and hypoprothrombinemia (Factor II activity 2%, Factor II antigen 5%) was screened for the presence of alterations in his prothrombin gene. Direct sequencing of PCR fragments derived from the coding and flanking regions of the prothrombin gene, revealed that the patient was homozygous for an A-->G substitution in exon 3. This substitution predicts the replacement of Tyr44 (TAC) by Cys (TGC) in the prothrombin molecule. Both parents were found to be heterozygous for the same mutation. Further family studies revealed complete cosegregation of the mutation with the prothrombin deficiency. Only the five homozygous brothers and sisters of the propositus were clinically affected (severe hemorrhages including epistaxis, soft tissue, muscle and joint bleedings in all, and severe hemorrhages in the two women). The bleeding tendency therefore seems to inherit as an autosomal recessive trait.
一名患有严重出血倾向和低凝血酶原血症（凝血因子II活性2%，凝血因子II抗原5%）的患者接受了凝血酶原基因改变的筛查。对来自凝血酶原基因编码区和侧翼区的PCR片段进行直接测序，结果显示该患者在第3外显子存在A→G替换的纯合子。这种替换预示着凝血酶原分子中Tyr44（TAC）被Cys（TGC）取代。发现双亲均为同一突变的杂合子。进一步的家系研究显示该突变与凝血酶原缺乏完全共分离。只有先证者的5个纯合子兄弟姐妹有临床症状（所有人均有严重出血，包括鼻出血、软组织、肌肉和关节出血，两名女性有严重出血）。因此，出血倾向似乎作为常染色体隐性性状遗传。
