Compound Heterozygosity for Two Novel Missense Mutations in the Prothrombin Gene in a Patient with a Severe Bleeding Tendency

S R Poort; R Landolfi; R M Bertina

doi:10.1055/s-0038-1656020

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1997; 77(04): 610-615
DOI: 10.1055/s-0038-1656020

Clinical Studies

Schattauer GmbH Stuttgart

Compound Heterozygosity for Two Novel Missense Mutations in the Prothrombin Gene in a Patient with a Severe Bleeding Tendency

S R Poort

¹The Hemostasis and Thrombosis Research Center, Department of Hematology, University Hospital Leiden, Leiden, The Netherlands

,

R Landolfi

²Instituto di Semeiotica Medica, Facoltà di Medicina e Chirurgia “Agostino Gemelli”, Università Cattolica del Sacro Cuore, Roma, Italy

,

R M Bertina

¹The Hemostasis and Thrombosis Research Center, Department of Hematology, University Hospital Leiden, Leiden, The Netherlands

› Author Affiliations

Abstract

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Summary

The abnormal prothrombin gene of an Italian patient with a severe bleeding tendency and hypoprothrombinemia was selected for study and compared with the prothrombin genes of healthy controls. All the coding and their flanking regions and the 5ʹ- and 3ʹ-UT regions of the prothrombin gene were screened by analyzing the nucleotide sequence of the corresponding PCR products. The patient was found to be heterozygous for two novel point mutations: one at nucleotide 4251 in exon 6, which changes the codon for cysteine-138 (TGC) in the kringle 1 domain to that for tyrosine (TAC), and one at nucleotide 8812 in exon 10, which results in the replacement of tryptophan-357 (TGG) by cysteine (TGT) in the catalytic domain. Her mother was heterozygous for the Cys-138 Tyr mutation and her father heterozygous for the Trp-357 Cys mutation. Several other sequence variations were identified in the prothrombin genes from control individuals. Only the variations at nucleotide 4203 and 10253 could be established as polymorphisms.

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References

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