Genetic Analysis of Afibrinogenemia and Hypofibrinogenemia: Novel Mutations in the <b><i>FGB</i></b> Gene in the Turkish Population

Abstract

Introduction: Congenital afibrinogenemia is a rare autosomal recessive disorder characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Hypofibrinogenemia is characterized by fibrinogen levels &lt;1.5 g/L. Objective: In this study, we analyzed fibrinogen beta chain gene mutations in Turkish afibrinogenemia and hypofibrinogenemia patients. Methods: We evaluated 20 afibrinogenemia and hypofibrinogenemia patients and 80 healthy controls. We have sequenced all exons of the FGB gene using the DNA isolated from the peripheral blood samples of patients and controls. Results and Conclusion: We found a nonsense mutation in exon 4 at nucleotide 630 that encoded serine amino acid, and in the same exon a missense mutation of T to C at nucleotide 647, resulting in a transition from leucine to proline (p.L198P) in a child with hypofibrinogenemia. These mutations have been shown for the first time in the same patient of Turkish descent. Furthermore, there was a novel heterozygous guanine-to-adenine nucleotide change in exon 3. This caused the change of arginine amino acid to threonine amino acid at position 136 (p.A136T) in a protein, which has not been described in the literature before.

A missense variant in DGKG as a recessive functional variant for hepatic fibrinogen storage disease in Wagyu cattle

“…Hepatic fibrinogen storage disease (HFSD) is an endoplasmic reticulum storage disorder with unique histopathologic findings characterized by abnormal accumulation of fibrinogen in the hepatocyte cytoplasm 1 . In humans, fibrinogen‐positive cytoplasmic inclusions may be present in a variety of clinical conditions including chronic hepatitis B infection, chronic liver disease, 2 alpha‐1‐antitrypsin deficiency (OMIM 107400) associated with disease‐causing variants in SERPINA1 , 3‐5 and hypofibrinogenemia with hepatic storage (OMIM 202400) associated with disease‐causing variants in FGA , 6 FGB , 7 and FGG 8 . Fibrinogen‐positive cytoplasmic inclusions can be classified into 3 groups according to their morphologic and ultrastructural appearance 9 .…”