A Chinese family with congenital Dysfibrinogenemia carries a heterozygous missense mutation in FGA: Concerningthe genetic abnormality and clinical treatment

摘要

Objectives: Congenital dysfibrinogenemia is a rare hereditary disease characterized by normal antigen level but lower function level of fibrinogen. Patients with congenital dysfibrinogenemia usually present as bleeding and/or thrombotic events. In this study, we explored the genetic abnormality and clinical treatment of a Chinese family with dysfibrinogenemia.Methods: This study was conducted in Jan 2015 to Jan 2016 in the Second Medical College (Shenzhen People’s Hospital, Jinan University, Shenzhen, Guangdong Province, P.R. China. Coagulation function test were used to screen patients in this family. For all family members, DNA from peripheral blood was isolated. Whole-genome exon sequencing was carried out to screen possible mutations. And sanger sequencing was employed to further confirm the mutation in patients.Results: The proband is a woman who had anemia and increased menstruation. Hypofibrinogenemia was found after admission. However, a pulmonary embolism occurred after the fibrinogen replacement treatment. Whole exon sequencing was conducted afterward. A candidate mutation in FGA gene (c.103C>A) was identified and validated in the woman and in two siblings.Conclusion: From this case, we learned that1) point mutation of c.103C>A is the pathogenesis for congenital dysfibrinogemia in this family; 2) thromboprophylaxis should always be in consideration when fibrinogen replacement is conducted. Prospective studies are needed to determine the best fibrinogen replacement strategy in order to achieve adequate hemostasis while minimize risk of thrombosis.