中华医学遗传学杂志
中華醫學遺傳學雜誌
중화의학유전학잡지
CHINESE JOURNAL OF MEDICAL GENETICS
2011年
1期
10-13
,共4页
金艳慧%王明山%牛真珍%谢耀盛%谢海啸%杨丽红
金豔慧%王明山%牛真珍%謝耀盛%謝海嘯%楊麗紅
금염혜%왕명산%우진진%사요성%사해소%양려홍
遗传性凝血因子Ⅷ缺乏症%基因突变%血液凝固障碍
遺傳性凝血因子Ⅷ缺乏癥%基因突變%血液凝固障礙
유전성응혈인자Ⅷ결핍증%기인돌변%혈액응고장애
hereditary coagulation factor Ⅶ deficiency%gene mutation%blood coagulation disorders
目的 对1个姨表近亲结婚的遗传性凝血因子Ⅷ(coagulation factorⅦ,FⅦ)缺乏症家系进行基因突变检测,探讨其分子发病机制.方法 检测凝血酶原时间(prothrombin time,PT)、活化部分凝血活酶时间、纤维蛋白原、血浆凝血因子活性等指标以明确诊断;用DNA直接测序法对先证者及家系成员FⅦ基因的全部外显子及侧翼、5'和3'非翻译区进行分析,寻找基因突变,用反向测序证实所发生的突变.结果 先证者PT(30.9 s)和FⅦ活性(3%)明显异常,女儿、父亲和母亲的PT(分别为21.2 s、16.3 s和16.1 s)稍延长和FⅦ活性(分别为22%、25%和35%)减低,胞弟各指标均在正常范围内;先证者FⅦ基因第8外显子的11482位为纯合T→G导致氨基酸His348Gln;女儿、父亲和母亲为His348Gln杂合子,胞弟为正常野生型.结论 该遗传性FⅦ缺乏症家系为纯合子错义突变His348Gln,推测此突变遗传自近亲结婚具有该杂合子的父母.
目的 對1箇姨錶近親結婚的遺傳性凝血因子Ⅷ(coagulation factorⅦ,FⅦ)缺乏癥傢繫進行基因突變檢測,探討其分子髮病機製.方法 檢測凝血酶原時間(prothrombin time,PT)、活化部分凝血活酶時間、纖維蛋白原、血漿凝血因子活性等指標以明確診斷;用DNA直接測序法對先證者及傢繫成員FⅦ基因的全部外顯子及側翼、5'和3'非翻譯區進行分析,尋找基因突變,用反嚮測序證實所髮生的突變.結果 先證者PT(30.9 s)和FⅦ活性(3%)明顯異常,女兒、父親和母親的PT(分彆為21.2 s、16.3 s和16.1 s)稍延長和FⅦ活性(分彆為22%、25%和35%)減低,胞弟各指標均在正常範圍內;先證者FⅦ基因第8外顯子的11482位為純閤T→G導緻氨基痠His348Gln;女兒、父親和母親為His348Gln雜閤子,胞弟為正常野生型.結論 該遺傳性FⅦ缺乏癥傢繫為純閤子錯義突變His348Gln,推測此突變遺傳自近親結婚具有該雜閤子的父母.
목적 대1개이표근친결혼적유전성응혈인자Ⅷ(coagulation factorⅦ,FⅦ)결핍증가계진행기인돌변검측,탐토기분자발병궤제.방법 검측응혈매원시간(prothrombin time,PT)、활화부분응혈활매시간、섬유단백원、혈장응혈인자활성등지표이명학진단;용DNA직접측서법대선증자급가계성원FⅦ기인적전부외현자급측익、5'화3'비번역구진행분석,심조기인돌변,용반향측서증실소발생적돌변.결과 선증자PT(30.9 s)화FⅦ활성(3%)명현이상,녀인、부친화모친적PT(분별위21.2 s、16.3 s화16.1 s)초연장화FⅦ활성(분별위22%、25%화35%)감저,포제각지표균재정상범위내;선증자FⅦ기인제8외현자적11482위위순합T→G도치안기산His348Gln;녀인、부친화모친위His348Gln잡합자,포제위정상야생형.결론 해유전성FⅦ결핍증가계위순합자착의돌변His348Gln,추측차돌변유전자근친결혼구유해잡합자적부모.
Obiective To investigate the gene mutation and the molecular pathogenesis of an inherited coagulation factor Ⅶ (F Ⅶ ) deficiency pedigree with consanguineous marriage. Methods The diagnosis was validated by coagulant parameter assay on the prothrombin time (PT), activated partial thromboplastin time, fibrinogen and coagulation factor activity. F Ⅶ gene mutations were analyzed in the proband and other family members by direct DNA sequencing of the PCR products of all exons, exon-intron boundaries and 5' and 3' untranslated sequences. The mutations were confirmed by reverse sequencing.Results The values of PT and FⅦ activity in the proband were significantly abnormal, they were 30. 9 s and 3% respectively. The PT of her daughter, father and mother was slightly extended to 21.2 s, 16.3 s and 16. 1 s respectively, and the FⅦ activity was reduced to 22%, 25% and 35% respectively. The coagulant parameters of her younger brother were within normal range. Homozygous T→G transition at position 11482 in exon 8 was identified in the proband resulting in His348Gln, and heterozygosity for His348Gln was confirmed in her daughter and her parents, and the normal wild-type was observed in her younger brother. Conclusion Homozygous missense mutation of His348Gln was found in a pedigree of hereditary FⅦ deficiency. The mutation was inherited from her heterozygote parents.
