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Updated: Jun 3, 2026
13:08
Measurement of Factor V Activity in Human Plasma Using a Microplate Coagulation Assay
Published on: September 9, 2012
Three dominant-negative mutations in factor XI-deficient patients.
L Dai1, S Rangarajan, M Mitchell
1Haemostasis Research Unit, Centre for Haemostasis and Thrombosis, Guy's and St Thomas' NHS Foundation & Kings College London School of Medicine, London, UK.
Summary
Factor XI (FXI) deficiency can be inherited dominantly. Novel mutations in the F11 gene impair FXI secretion, impacting FXI-deficient patients. This suggests dominant-negative FXI mutations are more common than previously believed.
Area of Science:
- Genetics
- Molecular Biology
- Hematology
Background:
- Factor XI (FXI) deficiency, typically autosomal recessive, arises from F11 gene defects.
- The homodimeric structure of FXI can facilitate dominant-negative inheritance patterns.
Observation:
- Three novel missense mutations (Ala43Thr, Phe241Leu, Val403Met) were identified in the F11 gene of three unrelated patients.
- In vitro studies demonstrated these mutations significantly reduced extracellular secretion of mutant FXI without affecting synthesis.
Findings:
- Mutant FXI proteins (Ala43Thr, Phe241Leu, Val403Met) impaired the secretion of wild-type FXI by 75.9%, 68.6%, and 71.4%, respectively.
- These findings confirm dominant-negative effects on FXI secretion.
Implications:
- Dominant-negative mutations in FXI deficiency may be more prevalent in non-Ashkenazi Jewish populations than previously recognized.
- The unique dimeric structure of FXI contributes to these dominant-negative inheritance patterns.
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