El-Din Hamdy Mona Salah, Nasr Aml Soliman, Makhlouf Manal Mohamed, El-Saadany Zainab Ali, Samir Magy, Morgan Dalia Saber
Department of Clinical and Chemical Pathology, Faculty of Medicine, El-Kasr El-Aini Hospital, Cairo University, El-Manial, Cairo, Egypt.
Department of Pediatrics, Faculty of Medicine, Cairo University, Cairo, Egypt.
Mol Diagn Ther. 2016 Apr;20(2):151-9. doi: 10.1007/s40291-015-0185-9.
Hemophilias are a group of related bleeding disorders that show an X-linked pattern of inheritance. The clinical phenotype of severe hemophilia may vary markedly among patients as a result of many factors, including genetic prothrombotic risk factors.
Our objective was to study the incidence of the most common prothrombotic risk factors for additive effects among Egyptian patients with hemophilia A and their impact on clinical phenotype; annual bleeding frequency and severity of hemophilic arthropathy, as well as the effect of a single variation in these patients.
This study was carried out in 100 patients with hemophilia A. Genotyping for factor V Leiden (FVL) G1691A, prothrombin G20210A, MTHFR C677T, and A1298C mutations was conducted using a real time-polymerase chain reaction (RT-PCR) assay.
Our study revealed mutations in hemophilia patients as follows: prothrombin G20210A (3 %), FVL (14 %), MTHFR C677T (42 %), and A1298C (59 %). Despite a lack of statistical significance when each gene was analysed separately, heterozygosity of prothrombin G20210A or FVL was always associated with either a mild or moderate, but never a severe, clinical presentation. The lowest bleeding frequency (less than once per month) was identified among patients with two heterozygous variants irrespective of the involved genes. In addition, the incidence of hemarthrosis was significantly higher among patients with a wild genotype of the prothrombin gene and FVL, and the average number of affected joints was significantly higher among patients with wild-type prothrombin and FVL genes than among heterozygous patients.
These prothrombotic mutations have a cumulative effect in amelioration of the severity of bleeding in hemophiliacs. The most prominent effect is that of prothrombin G20210A and FVL, while MTHFR C677A and A1298C gene mutations are less conclusive.
血友病是一组相关的出血性疾病，呈X连锁遗传模式。由于包括遗传性血栓形成危险因素在内的多种因素，严重血友病患者的临床表型可能有显著差异。
我们的目的是研究埃及甲型血友病患者中最常见的血栓形成危险因素的叠加效应发生率及其对临床表型的影响；年度出血频率和血友病性关节病的严重程度，以及这些患者中单一变异的影响。
本研究对100例甲型血友病患者进行。使用实时聚合酶链反应（RT-PCR）检测法对凝血因子V莱顿（FVL）G1691A、凝血酶原G20210A、亚甲基四氢叶酸还原酶（MTHFR）C677T和A1298C突变进行基因分型。
我们的研究揭示血友病患者的突变情况如下：凝血酶原G20210A（3%）、FVL（14%）、MTHFR C677T（42%）和A1298C（59%）。尽管分别分析每个基因时缺乏统计学意义，但凝血酶原G20210A或FVL的杂合性总是与轻度或中度临床表现相关，但从未与严重临床表现相关。在有两个杂合变异的患者中，无论涉及何种基因，出血频率最低（每月少于一次）。此外，凝血酶原基因和FVL野生基因型患者的关节积血发生率显著更高，野生型凝血酶原和FVL基因患者的平均受累关节数比杂合患者显著更高。
这些血栓形成突变在改善血友病患者出血严重程度方面具有累积效应。最显著的影响是凝血酶原G20210A和FVL，而MTHFR C677A和A1298C基因突变的结论性较低。
