背景:先天性纤维蛋白原疾病(CFDs)是由FGA突变引起的,FGB和FGG基因分为定量和定性纤维蛋白原缺陷。这项研究旨在确定伊朗CFDs的遗传背景,并检查基因型-表型相关性。
方法:纳入14例诊断为CFD的患者。分别通过免疫比浊法和Clauss方法测量纤维蛋白原抗原和活性。在纤维蛋白原基因的聚合酶链反应扩增后进行基因测序。还评估了所有病例的ISTH出血评估工具。
结果:患者被诊断为纤维蛋白原血症(n=10),低纤维蛋白原血症(n=2)和无纤维蛋白原血症(n=2)。位于FGA外显子2上的七个不同突变(57%),外显子4(7%),外显子5(7%)和FGG外显子8(29%)被鉴定。在定性不足的患者中,突变包括p.Arg38Thr,p.Arg35他,p.Arg35Cys,p.Val145Asp,和p.Arg301Cys,包括p.Gly316GlufsX105和p.Trp52stop。在纤维蛋白原血症中,两个热点突变,在60%的患者中鉴定出FGAArg35和FGGArg301,其余(40%)具有p.Arg38Thr突变。p.Val145Asp和两个热点突变,p.Arg35他,p.Arg35Cys,在伊朗首次被确认。所有患者的总体中位(范围)出血评分(BS)为4(0-6),纤维蛋白原血症为3.5(0-5)。皮肤出血和月经过多是最常见的出血表现。
结论:在CFDs中存在弱的基因型-表型相关性,并且与以前的研究相比,纤维蛋白原血症患者更有症状。尽管种族的差异,纤维蛋白原异常血症中热点突变的患病率与其他研究相似.
BACKGROUND: Congenital fibrinogen disorders (CFDs) are caused by mutations in the FGA, FGB and FGG genes and are classified as quantitative and qualitative fibrinogen defects. This study sought to determine the genetic background of CFDs in Iran and to examine the genotype-phenotype correlation.
METHODS: Fourteen patients with a CFD diagnosis were included. Fibrinogen antigen and activity were measured by the immunoturbidimetric and Clauss methods respectively. Gene sequencing was performed following a polymerase chain reaction amplification of fibrinogen\'s genes. The ISTH Bleeding Assessment Tool was also evaluated for all cases.
RESULTS: Patients were diagnosed with dysfibrinogenemia (n = 10), hypodysfibrinogenemia (n = 2) and afibrinogenemia (n = 2). Seven different mutations located on FGA exon 2 (57 %), exon 4 (7%), exon 5 (7%) and FGG exon 8 (29 %) were identified. In patients with qualitative deficiencies, mutations were including p.Arg38Thr, p.Arg35His, p.Arg35Cys, p.Val145Asp, and p.Arg301Cys and were including p.Gly316GlufsX105 and p.Trp52stop in afibrinogenemic patients. In dysfibrinogenemia, two hotspot mutations, FGA Arg35 and FGG Arg301 were identified in 60 % of patients and the remaining (40 %) had p.Arg38Thr mutation. The p.Val145Asp and two hotspot mutations, p.Arg35His, p.Arg35Cys, were identified for the first time in Iran. The overall median (range) bleeding score (BS) was 4 (0-6) in all patients and it was 3.5 (0-5) in dysfibrinogenemia. Cutaneous bleeding and menorrhagia were the most common bleeding manifestations.
CONCLUSIONS: There was a weak genotype-phenotype correlation in CFDs and patients with dysfibrinogenemia were more symptomatic than in previous studies. Despite ethnic\'s differences, the prevalence of hotspot mutations in dysfibrinogenemia was similar to the other studies.