一例女性血友病A患者发病机制的探讨  

Pathogenetic mechanism for a female patient with hemophilia A

作　　者：陈加弟 林燕芳[1] 林晓岚[1] 陈万紫[1] 傅蔷[1] 黄慧芳[1] 

机构地区：[1]福建省血液病研究所,福建省血液病学重点实验室,福建医科大学附属协和医院,福州350001

出　　处：《中华医学遗传学杂志》2016年第3期344-348,共5页Chinese Journal of Medical Genetics

基　　金：国家和福建省临床重点专科建设项目

摘　　要：目的探讨1例血友病A（hemophilia A，HA）女性杂合患者患病的机制。方法应用倒位移位聚合酶链反应（inverse shifting—polymerase chain reaction，IS-PCR）检测FⅧ基因缺陷；采用人雄激素受体检测（human androgen receptor，HUMARA assay）方法检测X染色体是否为非随机性失活；采用G显带法分析外周血细胞核型。结果IS-PCR检测发现该患者FⅧ基因存在第22内含子远端倒位；HUMARA检测发现该患者X染色体为非随机性失活——母源X染色体比父源X染色体活性低，即携带有正常FⅧ基因的母源X染色体比携带有缺陷FⅧ基因的父源X染色体甲基化失活比率更高；G显带核型分析显示先证者染色体核型未见明显异常。结论该血友病A女性患者的患病机制可能是由于X染色体非随机性不平衡失活引起的。Objective To explore the pathogenetic mechanism for a female patient affected with hemophilia A （hemophilia A, HA）. Methods Potential genetic defect was detected with inverse shiftingpolymerase chain reaction （IS-PCR）. The pattern of X chromosome inactivation was determined with a human androgen receptor assay （HUMARA assay）. G-banded karyotyping was carried out to exclude potential chromosome aberrations. Results IS-PCR showed that the defect of FⅧgene was the distal type of intron 22 inversion. The HUMARA assay showed that the X chromosome inactivation was non-random, and that the mother＇ s X chromosome activity was lower than that of the father＇ s X chromosome which has carried the inverted FⅧ gene. No abnormalities were found with G-banded chromosomes. Conclusion The prevalence of female HA patient may be caused by non-random inactivation of X chromosomes.

关 键 词：血友病A FⅧ基因 倒位移位聚合酶链反应 人雄激素受体检测 随机性失活 

分 类 号：R554.1[医药卫生—血液循环系统疾病] R440[医药卫生—内科学]