全基因组外显子测序技术在遗传性纤维蛋白原异常家系致病基因的克隆鉴定中的应用

Application of whole genome exon sequencing technology in identifying clone of hereditary fibrinogen abnormality family pathogenic gene

目的研究采用全基因组外显子测序技术在遗传性纤维蛋白原异常家系致病基因鉴定中的应用价值。方法采集12例遗传性纤维蛋白原异常患者及其核心家庭成员外周血检测凝血指标,并提取其基因组DNA进行全基因组外显子测序,分析测序结果,探讨遗传性纤维蛋白原异常的分子机制。结果全基因组外显子测序结果显示:先证者A1、A4以及B2均为FGA基因g.1233G>A突变,A1的妹妹、A4的父亲以及B2的母亲均携带有相同的突变;A2、A7、B4和B5均为FGG基因g.10819G>A突变,家系成员中A2的母亲和外婆、A7的姐姐和女儿、B4的母亲和B5的母亲均携带有相同的突变;A3、A5、A6、B1和B3及其相关亲属共10例携带有FGB基因g.9692A>G突变。先证者及家系主要成员中发生Fg基因突变的成员APTT、PT和TT均明显延长,但Fg活性显著降低。结论遗传性纤维蛋白原异常可由多种Fg基因外显子突变导致,FGB和FGG外显子突变较为常见。

Objective To research the applicative value of whole genome exon sequencing technology in identifying clone of hereditary fibrinogen abnormality family pathogenic gene. Methods Peripheral blood of 12 patients with hereditary fibrinogen abnormality and core family members was collected to detect coagulation index. And genomic DNA was received whole genome exon sequencing. Test results were analyzed to explore molecular mechanism of hereditary fibrinogen abnormality, Results Results of whole genome exon sequencing technology showed probandA 1, A4, and B2 all had FGA gene g. 1233G〉A mutation. AI＇ s sister, A4＇ s father, and B2＇ s mother carried the same mutation. A2, A7, B4 and B5 all had FGA gene, g.10819G〉A mutation. A2＇ s mother and grandmother, A7＇ s sister and daughter, B4＇ s mother and BS＇ s mother carried the same mutation. A3, AS, A6, B1 and B3 and 10 people in their related family had FGA gene g.9692A〉G mutation. In proband and main family members, TT, PT and APTT of those with Fg gene mutation were all prolonged, Fg activity was significantly decreased. Conclusion Hereditary fibrinogen abnormality can be caused by the mutation of a variety of Fg genes, and the mutations of FGB and FGG exons are common.