复合杂合性蛋白C基因突变导致的遗传性蛋白C缺陷症家系分析  

Analysis of an hereditary protein C deficiency pedigree with compound heterozygous gene mutations

作　　者：杨丽红[1] 朱丽青[1] 杨小丽[1] 王明山[1] 李佳[1] 陈必成[1] 金艳慧[1] 张卓[1] 郑芳秀[1] 

机构地区：[1]浙江省温州医学院附属第一医院,325000

出　　处：《中华医学遗传学杂志》2012年第5期515-518,共4页Chinese Journal of Medical Genetics

基　　金：浙江省温州市科技计划资助项目（Y20090033）

摘　　要：目的对1个遗传性蛋白C（proteinC，PC）缺陷症家系进行蛋白C基因（proteinCgene，PROC）突变检测，探讨其分子发病机制。方法通过检测先证者及其家系成员（共4代15人）血浆蛋白C活性（proteinCactivity，PC：A）、蛋白C抗原含量（proteinCantigen，PC：Ag）及其他凝血指标进行表型分析；用PCR法扩增先证者PROC的9个外显子及其侧翼序列，PCR产物纯化后测序，发现突变位点则反向测序予以证实；针对先证者的突变位点，对其家系成员进行相应基因突变检测。结果先证者PC：A和PC：Ag明显降低，分别为26％和18．60％，家系中其他成员中有7人PC：A降低，6人PC；Ag降低。先证者的PROC第7外显子存在g．6128T〉G杂合错义突变导致P．Phe139Val，第9外显子存在g．8478G〉C杂合错义突变导致P．Asp255His；其祖母、父亲、三姑和四姑均存在g．6128T〉G杂合突变，母亲、二舅、妹妹和儿子均存在g．8478G〉C杂合突变。存在g．8478G〉C突变的成员PC：A下降明显。结论先证者PROCg．6128T〉G和g．8478G〉C突变分别来自其父系家族和母系家族，该复合杂合错义突变是导致遗传性PC缺陷症的分子基础。Objective To analyze genetic mutations and explore its molecular pathogenesis for an hereditary protein C （PC） deficiency pedigree. Methods The pedigree has included 15 individuals from 4 generations. Plasma levels of PC activity （PC ： A）, PC antigen （PC ： Ag） and other coagulant parameters were determined for members of the family. The 9 exons and intron-exon boundaries of protein C gene （PROC） of the proband were amplified with PCR and analyzed with direct sequencing. Detected mutations were confirmed with reverse sequencing. Corresponding PCR fragments from the family members were also directly sequenced. Results Plasma PC ： A and PC 〉 Ag for the proband was 26% and 18. 60%, respectively, both being lower than normal references. Seven members from the pedigree also had lower PC ： A, six had lower PC ： Ag. A compound heterozygous missense mutation, including a T〉G transition at position 6128 of exon 7, which results in Phe139Val, and a G〉C transition at position 8478 in exon 9, which results in Asp255His, were identified in the proband. The paternal grandma, father and two aunts were heterozygous for g. 612STAG, whilst the mother, the second uncle, sister and son were heterozygous for g. 8478G〉C. There were lower PC ： A in family members with g. 8478G〉C. Conclusion The proband had inherited two independent mutations of the PROC gene including g. 612STAG in exon 7 and g. 8478G〉 C in exon 9 from her father and mother, respectively. The resulting compound heterozygous mutation has caused a serious hereditary protein C deficiency.

关 键 词：蛋白C缺陷症 复合杂合基因突变 家系 

分 类 号：R596[医药卫生—内科学]