Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.
Hematology. 2020 Dec;25(1):502-506. doi: 10.1080/16078454.2020.1859249.
To identify potential mutations of the FXII gene () in a consanguineous marriage family with hereditary coagulation factor XII (FXII) deficiency, and it will improve the understanding of the pathogenesis involved in the disease.
The proband was a 58-year-old male who had chronic gastritis. He was found to have a significantly prolonged activated partial thromboplastin time (APTT) at 101.0s (reference range, 29.0-43.0 s) before .
The coagulation factor XII activity (FXII:C) and FXII antigen (FXII:Ag) were measured by one-stage clotting assay and enzyme-linked immunosorbent assay, respectively. The gene was amplified by polymerase chain reaction and sequenced. Mutation sites were further confirmed by reverse sequencing. The conservatism and possible impact of the amino acid substitution were analyzed by multiple bioinformatics tools, as well as 3D protein model analysis.
The proband had a prolonged APTT (101.0 s), whose FXII:C and FXII:Ag were obviously reduced, both at 1.0% (normal range, 72-113%). Gene sequencing revealed that he carried a homozygous missense mutation of Met527Ile. Family study showed that his mother, son and daughter carried a heterozygous Met527Ile. Bioinformatics and model analysis of the mutation indicated that Met527Ile may be detrimental and potentially alters the structure and the function of the protein.
The novel mutation Met527Ile could potentially account for the reduced activity of FXII in this family.
在一个具有遗传性凝血因子 XII（FXII）缺乏症的近亲结婚家族中，鉴定 FXII 基因（）的潜在突变，以提高对疾病相关发病机制的认识。
先证者为 58 岁男性，患有慢性胃炎。在就诊前，其激活部分凝血活酶时间（APTT）明显延长至 101.0s（参考范围：29.0-43.0s）。
采用一期凝固法检测凝血因子 XII 活性（FXII:C），酶联免疫吸附法检测 FXII 抗原（FXII:Ag）。采用聚合酶链反应扩增基因，并进行测序。通过反向测序进一步确认突变位点。利用多种生物信息学工具以及 3D 蛋白模型分析，分析氨基酸取代的保守性和可能的影响。
先证者 APTT 延长（101.0s），其 FXII:C 和 FXII:Ag 明显降低，均为 1.0%（正常范围：72-113%）。基因测序显示他携带 Met527Ile 纯合错义突变。家系研究显示，其母亲、儿子和女儿均携带 Met527Ile 杂合突变。突变的生物信息学和模型分析表明，Met527Ile 可能具有危害性，并可能改变蛋白的结构和功能。
该家族中 Met527Ile 新突变可能导致 FXII 活性降低。
