一个新的FGA突变导致的遗传性无纤维蛋白原血症家族的分析

Genetic Analysis of an Inherited Afibrinogenemia Family Caused by a Novel Frameshift Mutation in FGA

遗传性无纤维蛋白原血症是一种以血液中纤维蛋白原完全缺乏为特征的遗传性出血性疾病,是一种常染色体隐性遗传病。为了对1个遗传性无纤维蛋白原血症家族成员进行凝血功能检查及基因分析,采集了该家族3代6人的外周血,应用全自动血凝仪检测活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)及纤维蛋白原(FG,Clauss法),并应用免疫比浊法测定纤维蛋白原抗原。以DNA提取试剂盒提取先证者及其他家族成员DNA,应用PCR法扩增FGA、FGB及FGG基因编码区、侧翼序列及启动子区。通过直接DNA测序方法检测基因突变。结果表明:先证者的父母为3代近亲。先证者FGA基因发现为纯合突变c.934-935insA,造成蛋白序列改变p.Ser312fsX42。先证者父母、祖母、外祖母及姑母均为该突变的杂合子携带者。该突变为国际上首次报道。结论:FGAc.934-935insA纯合突变是先证者发病的原因,该突变是1个新的FGA突变。

Inherited afibrinogenemia is a rare autosomal recessive bleeding disease characterized by complete absence of fibrinogen in blood. To identify the genotype in a Chinese family with inherited afibrinogenemia, the samples of peripheral blood were collected from 6 members of 3 generations. The activated partial thromboplastin time （ AFIT）, prothrombin time （FF）, thrombin time （TT） and fibrinogen （Fg, clauss） were tested. Fg was also analyzed by using immunoturbidimetry method. DNAs of six members were extracted by using a DNA extract kit. All the exons and exon- intron boundaries of the three fibrinogen genes were amplified by using PCR and analyzed by direct sequencing. The results showed that the parents of proband were 3 degree consanguinity. A homozygous c. 934_935insA in FGA was found in proband which results in the change of protein p. Ser312fsX42. The parents, grandmother, maternal grandmo- ther and father＇s sister were all detected with heterozygous mutation which was same as that in proband. In conclusion homozygous c. 934_935insA in FGA is a cause of inherited afibrinogenemia and a novel mutation being reported.