SERPINC1 variants causing hereditary antithrombin deficiency in a Danish population

Area of Science:

• Genetics
• Hematology

Background:

• Antithrombin deficiency increases the risk of venous thromboembolism (VTE).
• Identifying genetic causes is crucial for understanding VTE risk.

Purpose of the Study:

• To identify genetic variants responsible for hereditary antithrombin deficiency in a Danish population.
• To investigate the combined risk of type II heparin binding site (HBS) antithrombin deficiency and factor V Leiden.

Main Methods:

• Sanger sequencing and multiplex ligation-dependent probe amplification were used.
• Genotyping for factor V Leiden was performed in carriers of type II HBS deficiency.

Main Results:

• Causal variants were detected in all 46 individuals with antithrombin deficiency.
• Type I and various types of type II antithrombin deficiency variants were identified.
• Type II HBS deficiency, often due to p.(Pro73Leu) SNV, was most common; 12% of these carriers also had factor V Leiden.

Conclusions:

• A 100% variant detection rate was achieved in identifying hereditary antithrombin deficiency in the Danish cohort.
• The findings contribute to understanding the genetic landscape of antithrombin deficiency and associated VTE risk.