Owaidah Tarek M, Alkhail Hala Aba, Zahrani Hazzaa Al, Musa Abdulrahaman Al, Saleh Mahasen Al, Riash Mahmoud Abu, Alodaib Ali, Abu Amero Khalid
Departments of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.
Blood Coagul Fibrinolysis. 2009 Sep;20(6):415-8. doi: 10.1097/MBC.0b013e328329e456.
Different types of mutations have been reported in patients with hemophilia A. Although about half of all severe factor VIII deficiencies are caused by gene rearrangements (inversions) involving intron 22 in F8, other mutations such as point mutation, large deletions and insertions had been reported. We report the result of the first molecular testing for or F8 mutations from Saudi Arabia. A cohort of 22 men with hemophilia A was studied for F8 mutations. All patients were tested for factor VIII coagulant activity and inhibitors. Peripheral blood samples were used for DNA extraction followed by PCR detection of intron 22 inversion and all samples tested negative were screened for other F8 mutations. The patient's age ranged between 4 and 37 years. All patients except two siblings had severe hemophilia A. Only two patients out of 22 developed inhibitors with no obvious relation to the genotype. F8 Intron 22 inversion was detected in 10 patients (50%) of severe cases. Additionally, five point mutations and one deletion/insertion involving different exons were detected. All identified mutations were associated with severe phenotype except for one, which was associated with mild phenotype of hemophilia. This is the first report of molecular genotype of hemophilia A in the Saudi population and one of the few for Arab population. We had confirmed the incidence of Inversion 22 in severe hemophilia. We are reporting two novel mutations in F8, which can be used for carrier detection and prenatal genetic diagnosis (PGD).
血友病A患者中已报道了不同类型的突变。虽然所有严重的凝血因子VIII缺乏症中约有一半是由涉及F8基因内含子22的基因重排（倒位）引起的，但也有其他突变的报道，如点突变、大片段缺失和插入。我们报告了沙特阿拉伯首例F8基因突变分子检测的结果。对一组22名血友病A男性患者进行了F8基因突变研究。所有患者均检测了凝血因子VIII促凝活性和抑制物。采集外周血样本进行DNA提取，随后通过PCR检测内含子22倒位，对所有检测为阴性的样本筛查其他F8基因突变。患者年龄在4岁至37岁之间。除两名兄弟外，所有患者均为严重血友病A。22名患者中只有两名产生了抑制物，且与基因型无明显关联。在10名（50%）严重病例患者中检测到F8内含子22倒位。此外，还检测到五个点突变以及一个涉及不同外显子的缺失/插入。除一个与血友病轻度表型相关外，所有鉴定出的突变均与严重表型相关。这是沙特人群中血友病A分子基因型的首例报告，也是阿拉伯人群中为数不多的报告之一。我们证实了严重血友病中22号倒位的发生率。我们报告了F8基因的两个新突变，可用于携带者检测和产前基因诊断（PGD）。
