A familial study of a de novo FGG gene mutation causing congenital hypofibrinogenaemia and intervention during pregnancy and childbirth.

• Tác giả: Min Gao, Yarong Guo, Hongrui Li, Xiaoling Ma, Bin Mao, Jing Wang, Zehui Xie
• Ngôn ngữ: eng
• Thông tin xuất bản: England : Scientific reports , 2025
• Bộ sưu tập: NCBI
• ID: 741204

Tóm tắt

 To investigate the family line of a pregnant woman with congenital hypofibrinogenaemia due to a de novo mutation in the fibrinogen gamma (FGG) gene and experimentally explore its molecular pathological mechanisms. Peripheral blood specimens were collected from the proband and her family members for coagulation tests to assess their coagulation function. Whole exome sequencing was used to determine the gene mutation in the family lineage. SDS-PAGE was utilized to analyze the plasma of the proband and her mother for their congenital hypofibrinogenaemia. Structural distribution was analyzed by scanning electron microscopy. Molecular modeling was performed to predict the effect of mutation sites on fibrinogen structure and function. A de novo heterozygous mutation in the FGG gene was identified: c.702G >
  T, with a markedly prolonged thrombin time. The thromboelastography results showed that her fibrinogen function was essentially normal. LC-MS/MS showed no plasma or mutant chains in the plasma. Molecular modeling showed that this de novo mutation altered the structure of fibrinogen in the patient and her fibrinogen was heterogeneous in diameter and sparsely networked under electron microscopy. An intermittent infusion of 6 g of fibrinogen in the prenatal period of the proband brought the fibrinogen level of the patient to 2.13 g/L. No significant haemorrhage was detected between and after the caesarean section. The FGG gene NM_021870.3: c.702G >
  T (p.Trp234Cys) mutation is a de novo mutation, which is heterozygous in both the proband and her mother. It's the biogenetic basis for the pathogenicity of this congenital hypofibrinogenaemia family line.