Fibrinogen Barcelona II: a new case of A alpha 16 Arg----His substitution

Area of Science:

• Hematology
• Biochemistry
• Genetics

Background:

• Congenital dysfibrinogenemia represents a group of inherited disorders characterized by abnormal fibrinogen function.
• These disorders can lead to a range of clinical manifestations, including bleeding or thrombotic complications, though some cases are asymptomatic.

Observation:

• A novel fibrinogen variant, designated fibrinogen Barcelona II, was identified in eight members of a single family.
• No significant bleeding or thrombotic tendencies were reported in the affected individuals.

Findings:

• Incubation of fibrinogen Barcelona II with thrombin revealed an abnormal release pattern of fibrinopeptide A (FPA).
• Specifically, reduced release of normal FPA and delayed release of an abnormal FPA were observed.
• Purification and sequencing of the abnormal FPA identified a substitution of arginine with histidine at position 16 of the A alpha chain (A alpha 16 Arg----His).

Implications:

• This finding further elucidates the structure-function relationship of fibrinogen.
• The identified mutation (A alpha 16 Arg----His) provides a molecular basis for the abnormal behavior of fibrinogen Barcelona II.
• This case contributes to the understanding of the genetic and molecular basis of congenital dysfibrinogenemia.