Wang Jie, Li Qiang, Cheng Yan, Wang Aihui, Qiao Cuicui, Shao Jingru, Wang Tiantian, Wang Hehe, Zhang Xueqin, Poon Man-Chiu, Zhang Xinsheng, Fang Yunhai
Shandong Blood Center, Shandong Hemophilia Treatment Center, Jinan, China.
Central Hospital Affiliated to Shandong First Medical University, Jinan, China.
Ann Hematol. 2025 Jan;104(1):163-170. doi: 10.1007/s00277-024-06158-0. Epub 2024 Dec 26.
Hemophilia A (HA) is an X-chromosome-linked recessive genetic disorder. Female carriers may have bleeding symptoms, but rarely have moderate or severe disease. We identified a female patient with moderate HA by pedigree tracking and genetic testing in a HA family involving consanguineous marriage. To investigate the clinical and laboratory data, as well as F8 genetic variant affecting members in her family. We constructed a detailed pedigree diagram and performed coagulation analyses, including factor VIII activity (FVIII:C), FVIII inhibitor, and von Willebrand factor antigen (VWF: Ag) on 20 family members. The genomic DNA of 11 members was screened for intron 1 and intron 22 inversions using long-distance real-time polymerase chain reaction (RT-PCR). Their F8 coding genes were sequenced with an automatic next-generation sequencing. Thirteen HA persons with hemophilia (12 males, one female) and 18 female carriers were identified in the family. VWF: Ag level was normal in all 13 persons with hemophilia and 7 carriers tested. The female HA patient had FVIII:C 1.9 IU/dL and was homozygous for F8:c.1918G > T:p.V640F. Genetic testing is conducive to the diagnosis of hemophilia carriers and persons with hemophilia. F8: c.1918G > T:p.V640F is the pathogenic HA variant in this family. In any hemophilia family, we need to pay more attention to female carriers and patients.
甲型血友病（HA）是一种X染色体连锁隐性遗传病。女性携带者可能有出血症状，但很少有中度或重度疾病。我们通过家系追踪和基因检测，在一个涉及近亲结婚的HA家族中确定了一名中度HA女性患者。为了调查临床和实验室数据，以及影响其家族成员的F8基因变异。我们构建了详细的家系图，并对20名家庭成员进行了凝血分析，包括凝血因子VIII活性（FVIII:C）、FVIII抑制剂和血管性血友病因子抗原（VWF:Ag）。使用长距离实时聚合酶链反应（RT-PCR）对11名成员的基因组DNA进行内含子1和内含子22倒位筛查。他们的F8编码基因用自动下一代测序法进行测序。该家族中确定了13名血友病HA患者（12名男性，1名女性）和18名女性携带者。在所有接受检测的13名血友病患者和7名携带者中，VWF:Ag水平均正常。该女性HA患者的FVIII:C为1.9 IU/dL，F8:c.1918G > T:p.V640F为纯合子。基因检测有助于血友病携带者和血友病患者的诊断。F8:c.1918G > T:p.V640F是该家族中的致病性HA变异。在任何血友病家族中，我们都需要更多地关注女性携带者和患者。
