16例儿童先天性纤维蛋白原病的临床表型和基因型分析

Clinical phenotypes and genotypes of congenital fibrinogen disorder: an analysis of 16 children

摘要:

目的 分析先天性纤维蛋白原病（congenital fibrinogen disorder, CFD）患儿临床表型和基因型的特征。方法 回顾性分析16例CFD患儿的临床资料。聚合酶链反应技术扩增FGA、FGB、FGG基因全部外显子及侧翼序列并进行测序，分析变异特征。结果 16例患儿，男9例（56%），女7例（44%），中位就诊年龄4岁。9例（56%）患儿因出血事件就诊，7例（44%）因术前检查发现。出血事件患儿的纤维蛋白原活性水平低于无出血事件患儿（P<0.05）。12例患儿完成基因检测，共检出12种变异，其中有4个新位点变异，分别为FGA基因c.80T>C和c.1368delC、FGG基因c.1007T>A和c.1053C>A。2例遗传性无纤维蛋白原血症均为FGA基因无效变异引起，有较重的出血症状。7例遗传性异常纤维蛋白原血症主要由FGG和FGA基因杂合错义变异引起，临床表型从无症状至不同程度出血。结论 CFD患儿临床表现具有异质性，患儿出血的严重程度与纤维蛋白原活性水平有关，但临床表型与基因型之间的相关性较弱。

Abstract:

Objective To investigate the clinical phenotypes and genotypes of children with congenital fibrinogen disorder (CFD).Methods A retrospective analysis was conducted on the clinical data of 16 children with CFD. Polymerase chain reaction was used to amplify all exons and flanking sequences of the FGA, FGB, and FGG genes, and sequencing was performed to analyze mutation characteristics.Results Among the 16 children, there were 9 boys (56%) and 7 girls (44%), with a median age of 4 years at the time of attending the hospital. Among these children, 9 (56%) attended the hospital due to bleeding events, and 7 (44%) were diagnosed based on preoperative examination. The children with bleeding events had a significantly lower fibrinogen activity than those without bleeding events (P<0.05). Genetic testing was conducted on 12 children and revealed a total of 12 mutations, among which there were 4 novel mutations, i.e., c.80T>C and c.1368delC in the FGA gene and c.1007T>A and C.1053C>A in the FGG gene. There were 2 cases of congenital afibrinogenemia caused by null mutations of the FGA gene, with relatively severe bleeding symptoms. There were 7 cases of congenital dysfibrinogenemia mainly caused by heterozygous missense mutations of the FGG and FGA genes, and their clinical phenotypes ranged from asymptomatic phenotype to varying degrees of bleeding.Conclusions The clinical phenotypes of children with CFD are heterogeneous, and the severity of bleeding is associated with the level of fibrinogen activity, but there is a weak association between clinical phenotype and genotype.