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目的 探讨一个遗传性FⅦ缺乏症家系的基因突变类型。方法 检测FⅦ∶Ag、FⅦ∶C、FⅦa,并对缺陷进行分型 ;用DNA直接测序法对先证者及其家庭成员FⅦ基因的全部外显子及其侧翼进行分析 ;用蛋白质分子模型模拟软件对基因突变的生物结构病理学进行分析。结果 先证者FⅦ基因外显子 8的 115 14位为纯合子C→T导致氨基酸Thr35 9Met;父母及其子均为杂合子Thr35 9Met;Thr35 9Met导致CRM 型缺陷 ;蛋白质空间构型模拟分析发现 ,Thr35 9Met导致蛋白质空间构型发生改变 ,有较大侧链的Met置换了Thr后引起空间位阻 ,同时氢键数目也发生改变。结论 该遗传性FⅦ缺乏症家系为纯合子错义突变Thr35 9Met;推测此突变影响了蛋白质分子的空间构型 ,从而产生异常FⅦ蛋白的功能。
Objective To investigate the gene mutation types of a hereditary FⅦ deficiency family. Methods FⅦ: Ag, FⅦ: C and FⅦa were detected by FACS and their defects were genotyped. All the exons and flanks of FⅦ gene in probands and their family members were analyzed by DNA direct sequencing. The protein molecular model was used to simulate The software analyzes the biological structural pathology of mutations. Results The homozygote C → T of exon 8 in FⅦ gene of proband was homozygous for Thr35 9Met, Thr35 9Met was a heterozygous for both parents and its offspring, and Thr35 9Met resulted in CRM deficiency. The spatial structure of protein showed that , Thr35 9Met lead to changes in the spatial configuration of the protein, with a larger side chain Met replaced Thr caused steric hindrance, while the number of hydrogen bonds also changed. Conclusion This hereditary FⅦ deficiency family is homozygous missense mutation Thr35 9 Met. It is speculated that this mutation affects the spatial configuration of protein molecules and thus produces abnormal FⅦ protein.