CAJ | 학술논문

目的：对一个遗传性凝血因子Ⅻ（FⅫ）缺陷症家系进行FⅫ基因突变的分析和家系调查，探讨其分子发病机制。方法检测先证者及其家系成员活化部分凝血活酶时间（ APTT）、凝血酶原时间（ PT）、凝血因子Ⅷ活性（ FⅧ：C）、凝血因子Ⅸ活性（ FⅨ：C）、FⅪ活性（ FⅪ：C）、凝血因子Ⅻ活性（ FⅫ：C）和FⅫ抗原（ FⅫ：Ag）含量等进行表型诊断；用DNA直接测序法分析先证者FⅫ基因所有14个外显子、侧翼、5′和3′非翻译区及家系成员相应的突变位点区域，用反向测序证实所发生的突变。选择100名健康体检者作对照。结果先证者APTT明显延长为106．4 s，先证者二女儿和外孙女APTT略延长，分别为42．8 s和43．6 s，家系其他成员APTT无明显延长；先证者及其儿子、大女儿、二女儿、外孙女的FⅫ：C明显减低，分别为2．0％、23．0％、23．0％、24．0％和23．0％，FⅫ：Ag含量分别为1．0％、21．0％、23．0％、23．0％和23．0％，表现为交叉反应物质（ CRM）阴性。基因测序发现先证者FⅫ基因启动子区为46T／T型及13号外显子存在c．1556T＞G纯合突变，导致Leu519Arg；先证者儿子、大女儿、二女儿及外孙女为46C／T型，并且发现存在c．1556T＞G杂合突变；先证者妻子启动子区C／C型，且无上述基因突变。结论该家系发现的FⅫ基因13号外显子区c．1556T＞G尚未见报道。 c．1556T＞G影响了FⅫ催化功能，与FⅫ水平的降低有关。（中华检验医学杂志，2015，38：466－469）
목적：대일개유전성응혈인자Ⅻ（FⅫ）결함증가계진행FⅫ기인돌변적분석화가계조사，탐토기분자발병궤제。방법검측선증자급기가계성원활화부분응혈활매시간（ APTT）、응혈매원시간（ PT）、응혈인자Ⅷ활성（ FⅧ：C）、응혈인자Ⅸ활성（ FⅨ：C）、FⅪ활성（ FⅪ：C）、응혈인자Ⅻ활성（ FⅫ：C）화FⅫ항원（ FⅫ：Ag）함량등진행표형진단；용DNA직접측서법분석선증자FⅫ기인소유14개외현자、측익、5′화3′비번역구급가계성원상응적돌변위점구역，용반향측서증실소발생적돌변。선택100명건강체검자작대조。결과선증자APTT명현연장위106．4 s，선증자이녀인화외손녀APTT략연장，분별위42．8 s화43．6 s，가계기타성원APTT무명현연장；선증자급기인자、대녀인、이녀인、외손녀적FⅫ：C명현감저，분별위2．0％、23．0％、23．0％、24．0％화23．0％，FⅫ：Ag함량분별위1．0％、21．0％、23．0％、23．0％화23．0％，표현위교차반응물질（ CRM）음성。기인측서발현선증자FⅫ기인계동자구위46T／T형급13호외현자존재c．1556T＞G순합돌변，도치Leu519Arg；선증자인자、대녀인、이녀인급외손녀위46C／T형，병차발현존재c．1556T＞G잡합돌변；선증자처자계동자구C／C형，차무상술기인돌변。결론해가계발현적FⅫ기인13호외현자구c．1556T＞G상미견보도。 c．1556T＞G영향료FⅫ최화공능，여FⅫ수평적강저유관。（중화검험의학잡지，2015，38：466－469）
To analyze the mutations of F12 genein one pedigree with congenital factor FXII (FXII) deficiency , and investigatethe molecular mechanisms of FXII deficiency . Methods Activated partial thromboplastin time(APTT),Prothrombin time(PT), FXII activity(FXII:C), FXII antigen(FXII:Ag) and other coagulant parameters were tested in the proband and his family members .5'and 3'UTR,all exons and their exon-intron boundaries of F12 gene were analyzed by direct sequencing .The detected mutations were confirmed by reverse sequencing .100 healthy persons were as normal controls .Results The proband showed a markedly prolonged APTT (106.4s), the FXII:C and FXII:Ag were 2.0% and 1.0%, respectively .Hissecond daughter and granddaughter had slightly prolonged APTT , and other family members are normal.The FXII:C and FXII:Ag of family members were also decreased ( his son, 23.0% and 21. 0%;his elder daughter , 23.0%and 23.0%;his second daughter ,24.0%and 23.0%;hisgranddaughter , 23.0%and 23.0%).The phenotype of all members is consistent with cross -reactive material negative . Nucleotide sequencing analysis showed that the proband had missense mutations in the F 12 gene, including one homozygous mutationc.1556T >G ( p.Leu519Arg) and a commonly reported single nucleotide polymorphism site within the promoter region of the F 12 gene (46T/T) .Sequencing results from the proband 'children demonstrate them as carriers of a heterozygous missense mutation .The proband 's wife is normal and with 46C/C in the promoter region .Conclusion The c.1556T>G in exon 13 is a novel mutation .This mutation affects FXIIcatalytic function , associated with a reduced level of FXII .