Department of Pathology, College of Medicine, University of Sulaymaniyah, Sulaymaniyah, Iraq.
Charmo Center for Research, Training and Consultancy, Charmo University, Chamchamal, Sulaymaniyah, Iraq.
Clin Appl Thromb Hemost. 2020 Jan-Dec;26:1076029619888293. doi: 10.1177/1076029619888293.
Hemophilia A (HA) is a severe coagulation disorder affecting 1 in 5000 to 10 000 male births. In severe cases, the most deleterious large DNA rearrangements are inversions of intron 22 (Inv22) and intron 1 (Inv1) of the factor VIII (FVIII) gene. These account for 40% to 50% and 1% to 5% of all causative mutations, respectively. Nevertheless, no genetic analysis to identify the actual causative mutation of FVIII, particularly Inv22 and Inv1, among Iraqi Kurdish hemophiliacs has been performed. In this study, we aimed to genotype Inv22 and Inv1 of the FVIII gene in our patients with HA and reveal the genotype/phenotype correlation with the inversion mutations and their role as a risk factor for the development of inhibitors. Analyses of the Inv22 and Inv1 mutations in 80 Iraqi Kurdish patients with HA (60 severe, 18 moderate, and 2 mild) were performed using the inverse shifting-polymerase chain reaction (IS-PCR) method. In severe cases, 46.7% (28/60) had Inv22 and 3.3% (2/60) had Inv1. The genotype/phenotype relation of Inv22 and Inv1 illustrated a statistically significant association ( = .012) between disease severity and inversion mutations. Slightly more patients with Inv22 (39%) developed inhibitors than those without Inv22 (28%; odds ratio = 1.65, 95% confidence interval = 0.56-4.87, = .361). Inv22 is a major cause of severe HA in Iraqi Kurdish patients, and IS-PCR is a rapid, robust, and effective method that can be applied for carrier detection and prenatal diagnosis of HA in developing countries.
血友病 A (HA) 是一种严重的凝血障碍疾病，影响每 5000 至 10000 名男性出生中的 1 名。在严重的情况下，最具危害性的大 DNA 重排是因子 VIII (FVIII) 基因的内含子 22 (Inv22) 和内含子 1 (Inv1) 的反转。这些分别占所有致病突变的 40%至 50%和 1%至 5%。然而，在伊拉克库尔德血友病患者中，尚未进行任何遗传分析来确定 FVIII 的实际致病突变，特别是 Inv22 和 Inv1。在这项研究中，我们旨在对我们的 HA 患者的 FVIII 基因的 Inv22 和 Inv1 进行基因分型，并揭示与反转突变的基因型/表型相关性及其作为抑制剂发展的风险因素的作用。使用反向移位聚合酶链反应 (IS-PCR) 方法分析了 80 名伊拉克库尔德血友病患者（60 名严重，18 名中度和 2 名轻度）的 Inv22 和 Inv1 突变。在严重的情况下，46.7%（28/60）具有 Inv22，3.3%（2/60）具有 Inv1。Inv22 和 Inv1 的基因型/表型关系表明，疾病严重程度与反转突变之间存在统计学显著关联（=.012）。具有 Inv22 的患者（39%）比没有 Inv22 的患者（28%）更容易产生抑制剂（比值比= 1.65，95%置信区间= 0.56-4.87，=.361）。Inv22 是伊拉克库尔德患者严重 HA 的主要原因，IS-PCR 是一种快速、强大且有效的方法，可用于发展中国家 HA 的携带者检测和产前诊断。
