错义突变Thr318Met导致的遗传性凝血因子X缺陷症

Factor X Deficiency Resulted From a Missense Mutation Thr318Met in the FX Gene

目的对一个凝血因子X(FX)缺陷症家系进行FX基因突变的检测。方法用活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)及FX促凝活性 (FX :C)测定进行表型诊断 ;用PCR法对先证者的FX基因8个外显子及其侧翼序列和5’端非翻译区 (5’UTR)序列进行扩增 ,PCR产物纯化后直接测序 ,检测其基因突变。家系成员DNA在先证者FX基因突变区域扩增后测序。结果先证者表型诊断为FX缺陷症 ;FX外显子区共发现3个与文献报道的FX基因序列不同的位点 ,其中位于第8外显子区的为纯合突变C1098T。家系分析表明先证者父、母、弟和妹均为C1098T杂合子。结论纯合错义突变C1098T引起的Thr318Met是导致本例遗传性FX缺陷症的原因。

Objective To discover the gene mutations of a pedigree with inherited coagulation factor X(FX)deficiency.Methods The activated partial thromboplastin time(APTT),prothrombin time(PT)and FX ac-tivity(FX:C)test were adopted for phenotype diagnosis.The genomic DNA was extracted from the peripheral blood of the proposita.All the8exons,intron/exon boundaries and the5'untranslated regions(UTR)of the FX gene were amplified by polymerase chain reaction(PCR).The PCR products were screened by direct sequencing.The other4persons in the pedigree were examined too.Results Taking the FX nucleotide sequence published by Leytus as the reference,totally three variations in the FX gene have been found in the proposita.The missense mutation is a homozygous C1098T subtitution on exon8.Conclusions The FX deficiency of the proposita is caused by a homozygous Thr318to Met mutation in the FX gene.