[重型甲型血友病患者凝血因子 VIII 基因内含子 22 倒位的检测]

[Detection of intron 22 inversion of factor VIII gene in severe hemophilia A patients].

作者信息

Guo Zhi-ping, Chen Jian-fang, Qin Xiu-yu, Zhang Yao-fang, Yang Lin-hua

机构信息

Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2013 Nov;34(11):918-21. doi: 10.3760/cma.j.issn.0253-2727.2013.11.002.

DOI:10.3760/cma.j.issn.0253-2727.2013.11.002

PMID:24294844

Abstract

OBJECTIVE

To investigate the incidence of intron 22 inversion (INV22) of factor VIII (FVIII) gene in severe hemophilia A (HA) patients, clarify its pathological mechanism, and identify INV22 carrier in the female family members.

METHODS

One-stage method was used to assay the FVIII activity (FVIII:C)in 126 severe HA patients with a median age of 14 years old (range: 4 months-63 years). INV22 was analyzed by long-distance polymerase chain reaction (LD-PCR) and pulsed field gel electrophoresis (PFGE), and pedigree were conducted in 3 involved HA families.

RESULTS

Of all the 126 severe HA, 52 (41.3%) cases had the INV22. Four females including 3 mothers and 1 sister of probands were diagnosed as INV22 carriers among 11 suspected carrier mosaicisms from 3 INV22 positive HA families. In 8 females from one family without HA history, the patient's mother was a INV22 carrier, but her maternal grandmother, 2 maternal aunts, 2 female siblings and 1 elder female cousin were negative.

CONCLUSION

LD-PCR and PFGE could be used to diagnose severe HA patients with INV22 and identify the carriers.

摘要

目的

探讨重度甲型血友病（HA）患者凝血因子VIII（FVIII）基因内含子22倒位（INV22）的发生率，阐明其发病机制，并在女性家庭成员中鉴定INV22携带者。

方法

采用一期法检测126例重度HA患者的FVIII活性（FVIII:C），患者年龄中位数为14岁（范围：4个月至63岁）。通过长距离聚合酶链反应（LD-PCR）和脉冲场凝胶电泳（PFGE）分析INV22，并对3个受累的HA家系进行系谱分析。

结果

126例重度HA患者中，52例（41.3%）存在INV22。在3个INV22阳性HA家系的11名疑似携带者嵌合体中，4名女性（包括3名先证者的母亲和1名姐妹）被诊断为INV22携带者。在一个无HA病史家庭的8名女性中，患者的母亲是INV22携带者，但她的外祖母、2名姨母、2名女性兄弟姐妹和1名表姐均为阴性。