Wang Ming-shan, Jin Yan-hui, Zheng Fang-xiu, Xie Hai-xiao, Xu Peng-fei, Niu Zhen-zhen
Diagnosis Center of Clinical Laboratory, the First Hospital Affiliated to Wenzhou Medical College, Wenzhou 325000, China.
Zhonghua Xue Ye Xue Za Zhi. 2011 Dec;32(12):854-7.
To perform gene analysis and family survey of a patient with combined inherited FVII and FX deficiency, and to identify the gene mutation of this patient.
The phenotype diagnosis was validated by coagulant parameter assay on prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, FVII and FX activity (FVII:C, FX:C) and FVII and FX antigen (FVII:Ag, FX:Ag). FVII and FX gene mutations were analyzed in the proband and other family members by DNA direct sequencing of all exons, exon-intron boundaries and 5', 3' untranslated sequences. One hundred and six health examination participants were selected as control.
The values of PT and APTT of the proband showed significantly prolonged, which were 84.5s and 63.4s, respectively. The levels of FVII:C, FVII:Ag, FX:C and FX:Ag were 6%, 7%, 4% and 30%, respectively. The PT of his father, mother and sister was prolonged slightly while both APTT and FVII:Ag were in the normal range. Two homozygous mutations, g.11267C→T in exon 8 of FVII gene resulting in the substitution of Arg277Cys and g.28139G→T in exon 8 of FX gene leading to the substitution of Val384Phe, were identified in the proband. The proband's parents and sister were heterozygous for Arg277Cys and Val384Phe mutations.
Homozygous mutation Arg277Cys in FVII gene and Val384Phe in FX gene were the molecular mechanism causing combined inherited FVII and FX deficiency. The Val384Phe substitution was a novel mutation, which may affect the synthesis or secretion of FX protein.
对1例遗传性联合FⅦ和FⅩ缺乏症患者进行基因分析及家系调查，明确该患者的基因突变情况。
通过检测凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、纤维蛋白原、FⅦ和FⅩ活性（FⅦ：C、FⅩ：C）以及FⅦ和FⅩ抗原（FⅦ：Ag、FⅩ：Ag）等凝血参数对表型进行诊断。采用DNA直接测序法对先证者及其他家系成员的FⅦ和FⅩ基因所有外显子、外显子 - 内含子边界及5'、3'非翻译序列进行基因突变分析。选取106名健康体检者作为对照。
先证者PT和APTT值显著延长，分别为84.5秒和63.4秒。FⅦ：C水平为6%，FⅦ：Ag水平为7%，FⅩ：C水平为4%，FⅩ：Ag水平为30%。其父亲、母亲和妹妹的PT轻度延长，而APTT和FⅦ：Ag均在正常范围内。在先证者中鉴定出2个纯合突变，FⅦ基因第8外显子的g.11267C→T，导致Arg277Cys替换；FⅩ基因第8外显子的g.28139G→T，导致Val384Phe替换。先证者的父母和妹妹为Arg277Cys和Val384Phe突变的杂合子。
FⅦ基因的纯合突变Arg277Cys和FⅩ基因的Val384Phe是导致遗传性联合FⅦ和FⅩ缺乏症的分子机制。Val384Phe替换是一种新的突变，可能影响FⅩ蛋白的合成或分泌。
