中华医学遗传学杂志
中華醫學遺傳學雜誌
중화의학유전학잡지
CHINESE JOURNAL OF MEDICAL GENETICS
2014年
2期
134-139
,共6页
江明华%王晓欧%舒旷怡%蒋伟燕%黄颖%林颖%李珊珊%胡云良
江明華%王曉歐%舒曠怡%蔣偉燕%黃穎%林穎%李珊珊%鬍雲良
강명화%왕효구%서광이%장위연%황영%림영%리산산%호운량
遗传性异常纤维蛋白原血症%纤维蛋白原%凝血酶时间
遺傳性異常纖維蛋白原血癥%纖維蛋白原%凝血酶時間
유전성이상섬유단백원혈증%섬유단백원%응혈매시간
Inherited dysfibrinogenemia%Fibrinogen%Thrombin time
目的 分析8个遗传性异常纤维蛋白原血症家系的临床及基因突变特征.方法 用全自动血液凝固分析仪检测先证者及部分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),凝血酶时间(thrombin time,TT),纤维蛋白原(fibrinogen,Fg)活性,硫酸鱼精蛋白对TT的校正试验及凝血因子Ⅱ、Ⅴ、Ⅶ、Ⅷ、Ⅸ、Ⅹ、Ⅺ、Ⅻ的活性,D二聚体以及纤维蛋白(原)降解产物用免疫比浊法分析血浆中Fg抗原含量;用PCR法扩增先证者及家系成员纤维蛋白原基因FGA、FGB和FGG的所有外显子及其侧翼序列并测序,寻找基因突变.结果 8例遗传性异常纤维蛋白原血症先证者肝、肾功能、凝血因子Ⅱ、Ⅴ、Ⅶ、Ⅷ、Ⅸ、Ⅹ、Ⅺ、Ⅻ的活性均正常;PT及APTT正常或轻度延长;纤维蛋白(原)降解产物、D二聚体均正常;凝血酶时间明显延长,且硫酸鱼精蛋白不能使其明显缩短;Fg抗原含量均正常,但活性明显下降,Fg抗原含量/活性比值>2.8个家系中,1例为FGA基因g.1233G>A(p.AαArg35His)杂合突变,4例为FGB基因g.9692A>G(p.BβAsn190Ser)杂合突变,3例为FGG基因g.10819 G>A(p.γArg301His)杂合突变,此外还有2个多态性位点:FGA基因g.9308A/G(p.AαThr331Ala)多态性;FGB基因g.12628 G/A(p.BβArg478Lys)多态性.结论 8例遗传性异常纤维蛋白原血症先证者分别由p.AαArg35His、p.BβAsn190Ser和p.γArg301 His突变所致,其中p.BβAsn190 Ser国内未见报道,且p.BβAsn190Ser和p.γArg301 His可能为中国人的热点突变.
目的 分析8箇遺傳性異常纖維蛋白原血癥傢繫的臨床及基因突變特徵.方法 用全自動血液凝固分析儀檢測先證者及部分傢繫成員的凝血酶原時間(prothrombin time,PT),活化部分凝血活酶時間(activated partial thromboplastin time,APTT),凝血酶時間(thrombin time,TT),纖維蛋白原(fibrinogen,Fg)活性,硫痠魚精蛋白對TT的校正試驗及凝血因子Ⅱ、Ⅴ、Ⅶ、Ⅷ、Ⅸ、Ⅹ、Ⅺ、Ⅻ的活性,D二聚體以及纖維蛋白(原)降解產物用免疫比濁法分析血漿中Fg抗原含量;用PCR法擴增先證者及傢繫成員纖維蛋白原基因FGA、FGB和FGG的所有外顯子及其側翼序列併測序,尋找基因突變.結果 8例遺傳性異常纖維蛋白原血癥先證者肝、腎功能、凝血因子Ⅱ、Ⅴ、Ⅶ、Ⅷ、Ⅸ、Ⅹ、Ⅺ、Ⅻ的活性均正常;PT及APTT正常或輕度延長;纖維蛋白(原)降解產物、D二聚體均正常;凝血酶時間明顯延長,且硫痠魚精蛋白不能使其明顯縮短;Fg抗原含量均正常,但活性明顯下降,Fg抗原含量/活性比值>2.8箇傢繫中,1例為FGA基因g.1233G>A(p.AαArg35His)雜閤突變,4例為FGB基因g.9692A>G(p.BβAsn190Ser)雜閤突變,3例為FGG基因g.10819 G>A(p.γArg301His)雜閤突變,此外還有2箇多態性位點:FGA基因g.9308A/G(p.AαThr331Ala)多態性;FGB基因g.12628 G/A(p.BβArg478Lys)多態性.結論 8例遺傳性異常纖維蛋白原血癥先證者分彆由p.AαArg35His、p.BβAsn190Ser和p.γArg301 His突變所緻,其中p.BβAsn190 Ser國內未見報道,且p.BβAsn190Ser和p.γArg301 His可能為中國人的熱點突變.
목적 분석8개유전성이상섬유단백원혈증가계적림상급기인돌변특정.방법 용전자동혈액응고분석의검측선증자급부분가계성원적응혈매원시간(prothrombin time,PT),활화부분응혈활매시간(activated partial thromboplastin time,APTT),응혈매시간(thrombin time,TT),섬유단백원(fibrinogen,Fg)활성,류산어정단백대TT적교정시험급응혈인자Ⅱ、Ⅴ、Ⅶ、Ⅷ、Ⅸ、Ⅹ、Ⅺ、Ⅻ적활성,D이취체이급섬유단백(원)강해산물용면역비탁법분석혈장중Fg항원함량;용PCR법확증선증자급가계성원섬유단백원기인FGA、FGB화FGG적소유외현자급기측익서렬병측서,심조기인돌변.결과 8례유전성이상섬유단백원혈증선증자간、신공능、응혈인자Ⅱ、Ⅴ、Ⅶ、Ⅷ、Ⅸ、Ⅹ、Ⅺ、Ⅻ적활성균정상;PT급APTT정상혹경도연장;섬유단백(원)강해산물、D이취체균정상;응혈매시간명현연장,차류산어정단백불능사기명현축단;Fg항원함량균정상,단활성명현하강,Fg항원함량/활성비치>2.8개가계중,1례위FGA기인g.1233G>A(p.AαArg35His)잡합돌변,4례위FGB기인g.9692A>G(p.BβAsn190Ser)잡합돌변,3례위FGG기인g.10819 G>A(p.γArg301His)잡합돌변,차외환유2개다태성위점:FGA기인g.9308A/G(p.AαThr331Ala)다태성;FGB기인g.12628 G/A(p.BβArg478Lys)다태성.결론 8례유전성이상섬유단백원혈증선증자분별유p.AαArg35His、p.BβAsn190Ser화p.γArg301 His돌변소치,기중p.BβAsn190 Ser국내미견보도,차p.BβAsn190Ser화p.γArg301 His가능위중국인적열점돌변.
Objective To analyze clinical manifestation and genetic mutations in 8 Chinese pedigrees featuring hereditary dysfibrinogenemia.Methods Prothrombin time(PT),activated partial thromboplastin time(APTT),thrombin time(TT),calibration of plasma protamine sulfate against TT,fibrinogen (Fg) activity,coagulation factors Ⅱ,Ⅴ,Ⅶ,Ⅷ,Ⅸ,Ⅹ,Ⅺ and Ⅻ of all probands and their family members were detected with an automatic blood coagulation analyzer; D-dimer (D-D) and fibrin (ogen) degradation products(FDPs) were also dtected by automatic blood coagulation analyzer,Fg antigen were detected with an immunoturbidimetry method.Exons of fibrinogen genes FGA,FGB and FGG and flanking sequences were amplified by polymerase chain reaction(PCR) and sequenced.Results All of the probands showed normal levels of FDPs,D-dimer(D-D) and activity of coagulation factor Ⅱ,Ⅴ,Ⅶ,Ⅷ,Ⅸ,Ⅹ,Ⅺ,Ⅻ.Plasma PT and APTT were normal or slightly prolonged.Prolonged TT was found in all of the probands,whilst TT was not significantly shortened by protamine sulfate.Fg antigen was within the normal range,but Fg activity was significantly decreased.The Fg antigen/activity ratio was greater than 2.One proband has carried a heterozygous variant of the FGA gene g.1233G> A(p.AαArg35His).Four have carried a heterozygous mutation of the FGB gene g.9692A>G(p.BβAsn190Ser).The remaining 3 had heterozygous substitution of FGG gene g.10819G>A(p.γArg301His).In addition,2 polymorphisms (p.AαThr331Ala and p.BβArg478Lys) were identified in FGA and FGB genes.Conclusion p.AαArg35His,p.BβAsn190Ser and p.γArg301His are responsible for the inherited dysfibrinogenemia in the 8 Chinese pedigrees.p.BβAsn190Ser is firstly reported in China.p.BβAsn190Ser and p.γArg301His may be mutation hot spot in the Chinese population.