Identification of the First Iranian Family with “γArg275Cys” Mutation (Fibrinogen Tokyo II)

Abstract

Background: Inherited fibrinogen deficiencies areclassified into two categories: quantitative, including afibrinogenemia and hypofibrinogenemia and qualitative, including dysfibrinogenemia. Any mutation in fibrinogen genes accounts for one of these disorders. Case report: This article reports an Iranian family with dysfibrinogenemia without any clinical signs accidentally diagnosed by routin e coagulation tests with slightly elevated PT and APTT a few years ago. Fordeterminationof disease causing genetic aberration in fibrinogen genes, DNA sequencing of three hot spots of these genes (i.e. exon 2 of FGA,exon 2 of FGB and exon 8 of FGG)was performed. Analysis of sequencing results revealed a heterozygous missense mutation c.901 C>T (Arg275Cys) in exon 8 of FGG in mother and children.No mutationwas detected in father’s sample.Fibrinogen with this mutation is known as Tokyo II. Conclusion: γArg275Cys is a heterozygous mutation that impairs the function of fibrinogen andhas been solely reported in dysfibrinogenemic patients. Clinical findings in this family (no history of bleeding and thrombosis) were compatible with molecular results, because fibrinogen Tokyo II does not have a thrombotic or hemorrhagic nature and lack of clinical signs in this family is not unexpected.