背景:因子XII缺乏可能与F12基因中的纯合或复合杂合致病变体有关。该疾病通常被称为Hageman特征,并且以常染色体隐性或显性模式遗传。临床上,因子XII缺乏与出血无关,但与血栓事件有关,反复妊娠丢失,和遗传性血管性水肿.F12缺乏症的分子数据很少,并且在病例之间显示出不同的结果。然而,大多数报道的变异是错义突变,总删除,或小插入。在几项研究中已经报道了沙特人口中的XII因子缺乏,作为孤立病例报告或纳入罕见出血因素缺乏的研究。然而,缺乏分子数据,因为在我们的当地人群中没有发表与XII因子缺乏相关的遗传研究的病例报告,据我们所知.
方法:在本文中,我们描述了一名36岁的沙特多胎女性从外科诊所转诊的F12基因中涉及外显子12的纯合错义变异(5:176,830,269G>A;p.Gly506Asp),在术前评估袖状胃切除术时活化部分凝血活酶时间明显较高。患者在先前分娩期间没有出血发作史,也没有任何拔牙史。她在妊娠第15周发生了一次自然流产事件,没有任何出血并发症。无血栓病史或皮肤表现,她没有服用任何药物。无出血或血栓形成家族史。家族史显示出血缘关系,因为父母是一级表亲。体格检查不明显。经调查,活化部分凝血活酶时间延长通过1:1与正常池血浆混合研究得到完全校正,而狼疮抗凝试验为阴性.因子测定和血管性血友病因子测试均在正常范围内,除了因子XII,这是严重的缺陷。鉴定了涉及F12基因内外显子12的纯合错义变体(5:176,830,269G>A;p.Gly506Asp)。
结论:F12(5:176,830,269G>A;p.Gly506Asp)变异可能是纯合因子XII缺陷患者的致病变异。患者和家属的遗传咨询和管理应基于临床评估。
BACKGROUND: Factor XII deficiency can be related to either homozygous or compound heterozygous pathogenic variants in the F12 gene. The disease is commonly known as Hageman trait and is inherited in both autosomal recessive or dominant patterns. Clinically, factor XII deficiency is not associated with bleeding but conversely has been linked to thrombotic events, recurrent pregnancy loss, and hereditary angioedema. Molecular data of F12 deficiency are scarce and have revealed varying results between cases. However, most of the reported variants are missense mutations, gross deletions, or small insertion. Factor XII deficiency has been reported in the Saudi population in several studies, either as isolated
case reports or included within the studies of rare bleeding factors deficiency. However, molecular data are lacking as no
case report of genetic studies related to factor XII deficiency has been published in our local population, to the best of our knowledge.
METHODS: Herein we describe a homozygous missense variant involving exon 12 within F12 gene (5:176,830,269 G>A; p.Gly506Asp) in a 36-year-old Saudi multiparous female referred from the surgical clinic with significantly high activated partial thromboplastin time during preoperative assessment for sleeve gastrectomy. The patient had no history of bleeding episodes during the previous deliveries nor any tooth extractions. She had single event of spontaneous abortion during the 15th week of gestation without any bleeding complication. There was no history of thrombosis or skin manifestations, and she was not taking any medicines. There was no family history of bleeding or thrombosis. Family history revealed consanguinity as the parents are first-degree cousins. Physical examination was unremarkable. Upon investigation, the prolonged activated partial thromboplastin time was fully corrected by a 1:1 mixing study with normal pool plasma while lupus anticoagulant tests were negative. Factor assays and von Willebrand factor tests are all within normal ranges except for factor XII, which was severely deficient. A homozygous missense variant involving exon 12 within F12 gene (5:176,830,269 G>A; p.Gly506Asp) was identified.
CONCLUSIONS: F12 (5:176,830,269 G>A; p.Gly506Asp) variant is likely to be a pathogenic variant among homozygous factor XII-deficient patients. Genetic counseling and management of the patients and families should be based on clinical evaluation.