Thromb Haemost 1990; 64(03): 379-384
DOI: 10.1055/s-0038-1647323
Original Article
Schattauer GmbH Stuttgart

Two Mutations of the Factor IX Gene Including a Donor Splice Consensus Deletion and a Point Mutation in a Dutch Patient with Severe Hemophilia B

S R Poort
The Hemostasis and Thrombosis Research Unit, Department of Hematology, Leiden University Hospital, Leiden, The Netherlands
,
E Briët
The Hemostasis and Thrombosis Research Unit, Department of Hematology, Leiden University Hospital, Leiden, The Netherlands
,
R M Bertina
The Hemostasis and Thrombosis Research Unit, Department of Hematology, Leiden University Hospital, Leiden, The Netherlands
,
P H Reitsma
The Hemostasis and Thrombosis Research Unit, Department of Hematology, Leiden University Hospital, Leiden, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 01 December 1990

Accepted after revision 08 June 1990

Publication Date:
25 July 2018 (online)

Summary

The abnormal factor IX gene of a patient with severe hemophilia B (hemophilia B Ursem) was selected for study. All of the coding and their flanking regions and parts of the 5′- and 3′-untranslated regions of the factor IX gene were amplified from the patient’s genomic DNA by using the polymerase chain reaction (PCR). By analyzing the nucleotide sequence of the PCR products we have identified two mutations in the patient’s factor IX gene, viz. a tetranucleotide deletion (GAGT, nt 6492 to 6495) or (TGAG, nt 6491 to 6494) in the 5′-donor splice site consensus at the exon 2-intron B boundary, and a point mutation at nucleotide 31103 in the catalytic domain (exon 8) of factor IXa, which changes the codon for valine 328 (GTT) to one for isoleucine (ATT). PCR-amplified exon 8 from 45 normal males and 55 normal females had the codon for valine-328. We propose that the deletion within the donor splice-site consensus is the cause of the disease in this individual, whereas the substitution of valine-328 by isoleucine may be a neutral variant which is, at least, very rare in the normal population. In a family study the DNA sequence of the patient’s mother shows both the G to A transition in exon 8 and the 5′-donor splice consensus deletion in intron B in one allele.