Severe prekallikrein (Fletcher factor) deficiency due to a compound heterozygosis (383Trp stop codon and Cys529Tyr)

Anna Maria Lombardi; Maria Teresa Sartori; Laura Cabrio; Mariangela Fadin; Ezio Zanon; Antonio Girolami

doi:10.1160/TH03-05-0275

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2003; 90(06): 1040-1045
DOI: 10.1160/TH03-05-0275

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Severe prekallikrein (Fletcher factor) deficiency due to a compound heterozygosis (383Trp stop codon and Cys529Tyr)

Anna Maria Lombardi

¹Department of Medical and Surgical Sciences, 2^nd Chair of Internal Medicine, University of Padua Medical School, Padua, Italy

,

Maria Teresa Sartori

¹Department of Medical and Surgical Sciences, 2^nd Chair of Internal Medicine, University of Padua Medical School, Padua, Italy

,

Laura Cabrio

¹Department of Medical and Surgical Sciences, 2^nd Chair of Internal Medicine, University of Padua Medical School, Padua, Italy

,

Mariangela Fadin

¹Department of Medical and Surgical Sciences, 2^nd Chair of Internal Medicine, University of Padua Medical School, Padua, Italy

,

Ezio Zanon

¹Department of Medical and Surgical Sciences, 2^nd Chair of Internal Medicine, University of Padua Medical School, Padua, Italy

,

Antonio Girolami

¹Department of Medical and Surgical Sciences, 2^nd Chair of Internal Medicine, University of Padua Medical School, Padua, Italy

› Author Affiliations

Abstract

Summary

We investigated a family with prekallikrein deficiency, using both standard coagulation tests and molecular biology techniques. The propositus was found to be a compound heterozygote for a Trp383 stop codon and a Cys529Tyr point mutation. The former mutation was located in exon 11, the latter in exon 14. The propositus inherited the first defect from his father and the second from his mother. Both parents had slightly low prekallikrein levels, but the combination of the two genetic defects produced a phenotype characterized by an extremely low prekallikrein activity and antigen. The propositus’ plasma showed a progressive reduction in APTT when incubated for a long time. Conversely, plasma deficient in factor XII, factor XI or high molecular weight kininogen (HMWK) failed to show shortening of the APTT. No circulating anticoagulant was found because the patient’s APTT was fully corrected by pooled normal and factor XII-, factor XI- or HMWK deficient plasma. No associated abnormality was apparent in the propositus or his parents. As expected, no tendency for bleeding was noted even after tonsillectomy.

Keywords

Prekallikrein deficiency - Fletcher factor - contact phase - gene mutations

Full Text

References

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