Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Thromb Haemost. 2012 Oct;108(4):654-61. doi: 10.1160/TH12-02-0088. Epub 2012 Sep 5.
We report a rare case of congenital hypodysfibrinogenaemia due to maternal uniparental disomy of chromosome 4 (mat UPD 4) and a maternally inherited novel nonsense mutation Trp323X in the fibrinogen Bβ chain (FGB) gene. Western blot analysis of patient's plasma revealed an abnormal fibrinogen which consisted of truncated Bβ chain and normal Aα and γ chains. Patient's clinical history and laboratory evidence are presented. Microsatellite genotyping analysis revealed a mixed nature of heterodisomy and isodisomy along chromosome 4. High density SNP genotyping array analysis further confirmed the mat UPD 4 and defined two segments of chromosome 4 (4pter-p15.33 and 4q31.21-4q32.3) as maternal isodisomy (iUPD4) and the remaining regions as maternal heterodisomy (hUPD4), with the FGB gene carrying the mutation resided in the iUPD4 region on the long (q) arm. It was predicted that the segmental nature of iUPD and hUPD was caused by three recombination events at positions around 167.96 cM, 145.51 cM and 14.40 cM on chromosome 4 followed by a meiosis I non-disjunction. This case is clinically and molecularly unique and offers an opportunity for understanding novel mechanisms of congenital hypodysfibrinogenaemia associated with complex UPD and fibrinogen secretion.
我们报告了一例罕见的先天性低纤维蛋白原血症病例，该病例由母亲单亲二体性 4 号染色体（mat UPD 4）和母亲遗传的纤维蛋白原 Bβ 链（FGB）基因新的无义突变 Trp323X 引起。对患者血浆的 Western blot 分析显示异常纤维蛋白原由截断的 Bβ 链和正常的 Aα 和 γ 链组成。介绍了患者的临床病史和实验室证据。微卫星基因分型分析显示 4 号染色体存在杂合二体性和同二体性的混合性质。高密度 SNP 基因分型阵列分析进一步证实了 mat UPD 4，并确定了 4 号染色体的两个片段（4pter-p15.33 和 4q31.21-4q32.3）为母体同二体性（iUPD4），其余区域为母体杂合二体性（hUPD4），携带突变的 FGB 基因位于长（q）臂的 iUPD4 区域。据预测，iUPD 和 hUPD 的片段性质是由染色体 4 上大约 167.96 cM、145.51 cM 和 14.40 cM 位置的三个重组事件以及随后的减数分裂 I 非分离引起的。该病例在临床和分子上均具有独特性，为理解与复杂 UPD 和纤维蛋白原分泌相关的先天性低纤维蛋白原血症的新机制提供了机会。
