# Molecular mechanism analysis of a family with hereditary coagulation FⅪ deficiency caused by compound heterozygous mutations

## TL;DR

A family with hereditary coagulation FⅪ deficiency is analyzed, revealing compound heterozygous mutations that affect FⅪ activity and gene expression.

## Contribution

The study identifies and characterizes two novel compound heterozygous mutations in the F11 gene causing coagulation FⅪ deficiency.

## Key findings

- The p.Tyr351stop mutation significantly reduces F11 gene transcription.
- The p.Tyr503Cys mutation lowers FⅪ activity in cell culture supernatants despite normal transcription and protein expression.
- Family members show distinct inheritance patterns of the two mutations.

## Abstract

1例34岁女性患者因“乳房结节”拟行手术切除，术前检查发现活化部分凝血活酶时间（APTT）66.2 s、凝血因子Ⅺ活性（FⅪ∶C）2％、FⅪ抗原（FⅪ∶Ag）40.3％，患者及家系成员均无异常出血表现。诊断为遗传性凝血因子Ⅺ缺陷症。基因检测发现其F11基因第10外显子c.1107C>A（p.Tyr351stop）杂合无义突变、第13外显子c.1562A>G（p.Tyr503Cys）杂合错义突变，其父亲和儿子为p.Tyr351stop突变的杂合携带者，而母亲和女儿为p.Tyr503Cys突变的杂合携带者。体外表达结果显示，p.Tyr351stop突变导致F11基因转录水平显著降低，而p.Tyr503Cys突变对F11基因转录水平以及蛋白表达水平无影响，但该突变导致细胞培养上清液中FⅪ∶C水平显著降低。