Hereditary fibrinogen disorder is a rare kind of bleeding disease, which divided into two types. Type I is a kind of quantity disorder, including afibrinogenemia and hypofibrinogenemia. Type II is a kind of quality disorder, including dysfibrinogenemia. Fibrinogen is a kind of hexameric glycoprotein and consists of two pairs of three chains, which are Aα, Bβ and γchain. FGA、FGB and FGG code for the relevant glycoprotein. The mutations on these genes are responsible for this disorder. In this study, the levels of fibrinogen antigen of 12 cases with low fibrinogen activity were firstly detected. The results showed that one case had low level, and the patient definded as hypofibrinogenemia, and other 11 cases had normal level, thus these patients identified as dysfibrinogenemia. All exons and their flanks of FGA , FGB and FGG were amplified by PCR. THe PCR products were sequenced directly and blasted to normal sequence of corresponding gene to find the mutation. The result showed that among 11 cases with dysfibrinogenemia, five harbored Aα Arg16His heterozygous mutation and one of those also possessed a de novo γAsp185Asn heterozygous mutation ; one Aα Arg16Cys heterozygous mutation; four γArg275Cys heterozygous mutation and one γArg275His heterozygous mutation.The patient with hypofibrinogenemia harbored Aα Cys36Arg heterozygous mutation. Endonuclease restriction digestion was performed to exclude genetic polymorphism for the γAsp185Asn mutation. In molecular modeling, the hydrogen bonds were changed in the mutational variant of γ185Asn. Besides, a new site of glycosylation might appear after the mutation, which might lead to destroy the stability of molecular structure. The alignment of homologous sequence between different species suggested that γAsp185 was a highly conservative site. In a word, the above mutations might be the causes of dysfibrinogenemia or hypofibrinogenemia for these patients.


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Asterisk with author names denotes non-ASH members.

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