Phe139Val纯合突变所致遗传性蛋白C缺陷症近亲婚配家系  

Analysis of a hereditary protein C deficient consanguineous pedigree caused by Phe139Val homozygous mutation

作　　者：杨丽红[1] 朱丽青[1] 王莹宇 谢海啸[1] 谢耀盛[1] 金艳慧[1] 王明山[1] 陈必成[2] 杨小丽[1] 

机构地区：[1]温州医科大学附属第一医院临床实验诊断中心,325000 [2]温州医科大学附属第一医院移植中心实验室,325000

出　　处：《中华血液学杂志》2013年第9期767-770,共4页Chinese Journal of Hematology

基　　金：基金项目：浙江省温州市科技计划资助项目（H20110016、Y20100230）

摘　　要：目的探讨1个姨表近亲结婚遗传性蛋白C缺陷症家系的分子发病机制。方法对先证者及其家系成员（共3代8人）进行血浆蛋白C活性（PC：A）、蛋白C抗原（PC：Ag）含量及其他凝血指标检测；PCR扩增先证者蛋白C基因的9个外显子及其侧翼序列，产物纯化后直接测序；发现突变位点，再对其家系成员进行该位点的突变检测。结果先证者及其弟弟PC：A分别为20％和31％，PC：Ag分别为13．2％和18．9％，均明显降低；先证者及其弟弟蛋白C基因测序检出第7号外显子g．6128T〉G纯合错义突变导致Phe139Val，其他家系成员均为Phe139Val杂合突变。结论Phe139Val纯合突变是该家系遗传性蛋白C缺陷症的分子发病机制，可能与先证者父母近亲婚配有关。Objective To analyze genetic mutation and explore its molecular pathogenesis for an hereditary protein C （PC） deficient consanguineous pedigree. Methods The pedigree included three generations and contained eight members. PC activity （PC：A）, PC antigen （PC： Ag）and other coagulant parameters were detected for all family members. Protein C gene （PROC） include all the exons and intron- exon boundaries were amplified by PCR for the proband, then analyzed by direct sequencing. Mutation sites were detected for the other family members. Results The PC ： A and PC： Ag in the proband plasma were 20% （normal range 70% -140% ） and 13.2% （normal range 70%-130% ）. A homozygous missense mutation g.6128T〉G in exon 7 resulting in Phe 139Val was identified in the proband. The PC：A and PC ：Ag in her younger brother were 31% and 18.90%, Phe139Val homozygous was also found. The left family members were heterozygous for Phe139Val. Conclusion Phe139Val homozygous missense mutation in exon 7 of PROC caused serious hereditary protein C deficiency, We speculated that homozygous mutation might be resulted from this consanguineous marriage.

关 键 词：蛋白C缺乏 突变 系谱 近亲 遗传 

分 类 号：R596.1[医药卫生—内科学]