Antithrombin Krakow II (c.624+1 G > T): a novel mutation leading to type 1 antithrombin deficiency

Area of Science:

• Genetics
• Hematology
• Molecular Biology

Background:

• Hereditary antithrombin (AT) deficiency is a rare autosomal disorder.
• Over 200 mutations in the AT gene are known to cause AT deficiency.

Observation:

• A 26-year-old Polish man with type I AT deficiency presented with deep vein thrombosis and pulmonary embolism.
• The patient experienced thrombosis despite low-molecular-weight heparin prophylaxis and had a history of ankle trauma.
• Family history was negative for venous thromboembolism.

Findings:

• Antithrombin activity was 47-53%, and antigen level was 0.15 g/l.
• Genetic analysis revealed a novel heterozygous mutation (c.624 + 1 G > T) in the AT gene, named antithrombin Krakow II.
• The mutation is located at a splice site, suggesting potential functional impact.

Implications:

• This case highlights a new mutation causing hereditary antithrombin deficiency.
• The findings emphasize the importance of genetic analysis in diagnosing and managing thrombotic events.
• Understanding novel mutations aids in predicting thrombotic risk and tailoring prophylaxis.