Extension of the Human Fibrinogen Database with Detailed Clinical Information-The αC-Connector Segment

Area of Science:

• Biochemistry
• Genetics
• Hematology

Background:

• Fibrinogen is a key plasma glycoprotein in blood coagulation.
• Mutations in fibrinogen can lead to bleeding and thrombotic disorders.
• The Human Fibrinogen Database catalogs clinically relevant mutations.

Purpose of the Study:

• To extend the Human Fibrinogen Database for the αC-connector region (amino acids Aα240-410).
• To detail clinical manifestations, bleeding/thrombotic events, and coagulation assay results for family members with mutations.
• To report the impact of mutations on clotting and fibrinolysis.

Main Methods:

• Database extension with clinical data.
• Analysis of mutation types (missense, synonymous, nonsense, frameshift).
• Correlation of mutation location and type with clinical phenotypes.

Main Results:

• Homozygous nonsense or frameshift mutations in the αC-connector cause most clinically relevant symptoms.
• Heterozygous mutations are frequently asymptomatic.
• Symptomatic individuals experience bleeding, less commonly thrombotic events, miscarriages, and prolonged wound healing.
• Thrombotic phenotypes arise from mutations at specific tandem repeat positions.

Conclusions:

• The αC-connector region harbors clinically significant fibrinogen mutations.
• Mutation type (homozygous vs. heterozygous) and location dictate clinical presentation.
• Understanding these mutations aids in diagnosing and managing coagulation disorders.