山东省55例血友病A患者基因检测及分析

doi:10.6040/j.issn.1671-7554.0.2019.803

摘要/Abstract

摘要： 目的分析山东省55例血友病A(HA)患者基因突变类型,探讨HA发病机制。方法采用LD-PCR法检测山东省55例HA患者凝血因子Ⅷ(FⅧ)基因的内含子22倒位突变,阴性者采用高通量测序法检测FⅧ基因的26个外显子,并与人类基因突变数据库比对。结果 55例HA患者中内含子22倒位突变20例,其他35例共检测到28种突变类型,其中3例同时检测出2种突变,有6例未检测到基因突变。共发现c.2034_2062del、c.6052_6058del、c.6046_6047del、c.1009+1G>T、c.2997dupA、c.4001delT、c.1334T>A、c.1493G>A、c.557A>T等9种未被报道过的新突变。结论 FⅧ基因突变是导致HA的根本原因。重型血友病患者中最常见的突变类型为内含子22倒位突变。编码区突变最常见的突变类型为错义突变。新发现的9种新突变丰富了基因突变谱,为探讨HA发病机制提供了基础。

关键词: 血友病A, 凝血因子Ⅷ, 基因突变, 内含子22倒位, 基因测序

Abstract: Objective To analyze the genetic mutation types of 55 patients with hemophilia A(HA)in Shandong Province, and explore its molecular mechanism. Methods The intron 22 inversion mutation of factor Ⅷ(FⅧ)in all patients was detected with LD-PCR. The 26 exons of FⅧ negative patients were detected with next-generation sequencing and matched in the humangene mutation database. Results Of all 55 patients, 20 had intron 22 inversion mutation, and the other 35 had 28 different types of mutations, of whom 3 had 2 simultaneous mutations, while 6 had no mutation. Altogether 9 new mutation types unreported before were discovered, including c.2034_2062del, c.6052_6058del, c.6046_6047del, c.1009+1G>T, c.2997dupA, c.4001delT, c.1334T>A, c.1493G>A and c.557A>T. Conclusion FⅧ mutation is the direct cause of HA. The most common mutation in severe HA is intron 22 inversion mutation. The most common mutation in coding region mutation is the missense. The 9 new mutations discovered in the study enrich the gene mutation profile and provide reference for the study of HA pathogenesis.

Key words: Hemophilia A, Coagulation factor Ⅷ, Gene mutation, Intron 22 inversion, Gene sequencing

中图分类号:

R574

张文慧,陈昀,常亚丽,周亚伟,房云海,张心声,郭农建. 山东省55例血友病A患者基因检测及分析[J]. 山东大学学报 (医学版), 2019, 57(12): 57-61.

ZHANG Wenhui, CHEN Yun, CHANG Yali, ZHOU Yawei, FANG Yunhai, ZHANG Xinsheng, GUO Nongjian. Gene detection and analysis of 55 patients with hemophilia A in Shandong Province[J]. Journal of Shandong University (Health Sciences), 2019, 57(12): 57-61.

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