一个近亲结婚导致的遗传性凝血因子Ⅴ缺陷症家系的基因突变分析  

Analysis of a consanguineous pedigree featuring hereditary coagulation factor V deficiency

作　　者：谢耀盛[1] 张扬[1] 朱丽青[1] 金艳慧[1] 杨丽红[1] 谢海啸[1] 王明山[1] 杨小丽[1] 

机构地区：[1]温州医学院附属第一医院实验诊断中心,325000

出　　处：《中华医学遗传学杂志》2013年第2期161-164,共4页Chinese Journal of Medical Genetics

基　　金：浙江省教育厅科研基金资助项目（Y200906245）

摘　　要：目的对1个姨表近亲结婚的遗传性凝血因子V（coagulation factorV，FV）缺陷症家系进行基因分析，探讨其分子发病机制。方法检测先证者及其家系成员的凝血酶原时间（prothrombin time，PT）、活化部分凝血活酶时间（activated partial thromboplastin time, APTT）、纤维蛋白原（fibrinogen，FIB）、血浆FV活性（FV：C）和血浆FV抗原（FV：Ag）等凝血指标进行表型诊断。用DNA直接测序法分析先证者及家系成员F5基因的全部外显子及侧翼、5’和3’非翻译区，发现突变位点用反向测序予以证实。结果先证者PT和APTT均明显延长，分别为23．5S和50．5s，其FV：C（8％）和FV。Ag（〈1％）极度减低；同样先证者的妹妹PT和APTT也显著延长，分别为24．1s和62．4s，其FV：C（7％）和FV：Ag（〈1％）也极度减低；家系其他成员的PT及APTT均在正常参考范围。先证者的F5基因第5外显子测序发现其29170位为纯合突变T—C，导致190位氨基酸苯丙氨酸变为丝氨酸（Phel90Ser），先证者的妹妹同样为纯合Phe190Ser突变；大哥、大姐、大女儿、小女儿和外甥女均为Phel90Ser杂合突变，其FV：C也有所减低（分别为57％、73％、72％、66％、75％）；两个弟弟为正常野生型，其FV：C和FV：Ag均在正常水平。结论该遗传性FV缺陷症家系先证者及其妹妹F5基因第5外显子存在g．29170T—C纯合型错义突变，导致Phe190Ser。其原因推测与其父母近亲结婚有关。Phe190Ser与该遗传性凝血因子V缺陷症家系FV水平降低有关。Objective To screen potential mutation and explore the underlying mechanism for a consanguineous pedigree featuring hereditary coagulation factor V （F V ） deficiency. Methods Clinical diagnosis was validated by coagulant parameter assays of prothrombin time （PT）, activated partial thromboplastin time （APTT）, fibrinogen （FIB）, FV procoagulant activity （FV ： C） and FV antigen （FV ： Ag）. Potential mutations of the F5 gene in the proband and his family members were analyzed by direct DNA sequencing of PCR products of all exons, exon-intron boundaries and 3r, 51 untranslated regions. Suspected mutation was confirmed by reverse sequencing. Results The PT and APTT in the proband were significantly prolonged, which measured 23.5 s （reference range 11.8-14.8 s） and 50.5 s （reference range 27.0-41.0 s）, respectively. FV activity and FV antigen of the proband were significantly reduced to 8% and ; 1%, respectively. PT and APTT in the younger sister of the proband were also significantly prolonged （24. 1 s and 62. 4 s, respectively）. Her F V activity and F V antigen were also significantly decreased （7% and ; 1;, respectively）. PT and APTT of other family members were within normal range. The homozygous missence mutation causing T→C transition at position 29 170 in exon 5 of F5 gene has resulted in a Phe190Ser substitution in the proband. His younger sister was also homozygous for Phe190Ser. Heterozygosity for Phe190Ser was confirmed in his elder brother, elder sister, two daughters and niece, and their FV activity were slightly decreased （57%,73% ,72% ,66% and 75;, respectively） . A normal wild type was observed in two younger brothers of the proband, and their F V activity and F V antigen were in the normal range. Conclusion Homozygous missence mutation of Phel90Ser has been found in above family featuring hereditary FV deficiency. The homozygous missence mutation was inherited from the parents by consanguineous marriage. Phel90Ser probably underlies may underlie the patho

关 键 词：近亲结婚家系 凝血因子V缺陷症 基因突变 血液凝固障碍 

分 类 号：R5[医药卫生—内科学]