纯合变异导致遗传性蛋白S缺陷症一家系调查

A homozygous variant in a consanguineous pedigree with inherited protein S deficiency

目的观察一个纯合变异导致遗传性蛋白S缺陷症家系的临床特征,分析其PROS1基因的突变情况。方法采集先证者及其家系成员(3代6名)血标本,检测蛋白S水平,对先证者及家系成员进行PROS1基因筛查。PCR法扩增PS基因(PROS1基因)的15个外显子、侧翼序列及3′、5′非翻译区,PCR产物纯化后直接DNA测序。结果6名家系成员中5例确诊存在遗传性蛋白S缺陷症,先证者表现肺栓塞,其他患者尚未出现明显血栓事件。基因分析发现先证者第1外显子启动子区存在c.-168C>T纯合变异,其父亲、母亲、弟弟和儿子均为c.-168C>T杂合变异,妻子为野生型。结论本家系发现PROS1 c.-168C>T基因变异导致遗传性蛋白S缺陷症。遗传性蛋白S缺陷症是一种临床表现多变的易栓症,可反复出现深静脉血栓和(或)肺栓塞,需引起临床高度重视。

Objective To observe the clinical feature of familiar hereditary protein S deficiency,and to explore the related gene mutation.Methods The blood samples were obtained from the proband and the family memebers(3 generations,6 persons).PROS1 gene of the proband and the family members was analyzed.The 15 exons and flanking sequence of PROS1 gene were analyzed by PCR and DNA sequencing.Results Five out of 6 family members were diagnosed as having hereditary protein S deficiency.The proband suffered from pulmonary embolism.The others had no obvious thrombotic event.The gene sequencing revealed that the proband carried a c.-168C>T homozygous variant in the promoter of exon 1.His parents,brother and son all carried c.-168C>T heterozygosis variant at the same position.The gene of his wife was a wild type.Conclusion A gene variant(c.-168C>T)of PROS1 was discovered in this Chinese family.Gene variant of PROS1 may result in protein S deficiency.Patients with protein S deficiency may suffer from vein thrombosis and(or)pulmonary embolism.