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Thromb Haemost 1994; 72(06): 819-824
DOI: 10.1055/s-0038-1648968
Original Article
Schattauer GmbH Stuttgart

Homozygosity for a Novel Missense Mutation in the Prothrombin Gene Causing a Severe Bleeding Disorder

S R Poort
The Hemostasis and Thrombosis Research Center, Department of Hematology, University Hospital Leiden, Leiden, The Netherlands
,
J J Michiels
1   Department of Hematology, University Hospital Rotterdam, Rotterdam, The Netherlands
,
P H Reitsma
The Hemostasis and Thrombosis Research Center, Department of Hematology, University Hospital Leiden, Leiden, The Netherlands
,
R M Bertina
The Hemostasis and Thrombosis Research Center, Department of Hematology, University Hospital Leiden, Leiden, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 07 July 1994

Accepted after revision 30 August 1994

Publication Date:
06 July 2018 (online)

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Summary

A patient with a severe bleeding tendency and hypoprothrombin-emia (Factor II activity 2%, Factor II antigen 5%) was screened for the presence of alterations in his prothrombin gene. Direct sequencing of PCR fragments derived from the coding and flanking regions of the prothrombin gene, revealed that the patient was homozygous for an A ⟶ G substitution in exon 3. This substitution predicts the replacement of Tyr 44 (TAC) by Cys (TGC) in the prothrombin molecule. Both parents were found to be heterozygous for the same mutation. Further family studies revealed complete cosegregation of the mutation with the prothrombin deficiency. Only the five homozygous brothers and sisters of the propositus were clinically affected (severe hemorrhages including epistaxis, soft tissue, muscle and joint bleedings in all, and severe hemorrhages in the two women). The bleeding tendency therefore seems to inherit as an autosomal recessive trait.

 

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