title: Factor IX gene mutations in haemophilia B: a New Zealand population-based study.
abstract: Haemophilia B (Christmas disease) is an X-linked bleeding disorder resulting from an inherited deficiency of coagulation factor IX activity. Due to the heterogeneity of mutations within the factor IX gene there is a marked clinical variability in disease severity. By applying techniques of mutational analysis and direct sequencing of PCR products it is now potentially possible to determine the pathogenic gene defect in entire haemophilia B populations. We report here characterization of the factor IX gene defect in all the haemophilia B patients in New Zealand as part of a nationwide approach towards providing efficient and cost-effective haemophilia B genetic counselling services for these families. Twenty-six different mutations were identified in 32 unrelated haemophilia B families. Three defects at nucleotide positions +8,6659 and 17696 are novel mutations which have not been reported by other laboratories. A PCR-based diagnostic screening test for direct mutational analysis could be performed in most cases; 17 of the 26 mutations altered a restriction enzyme recognition sequence and, with the exception of the total gene deletion, base changes not affecting a restriction enzyme site could be detected by allele-specific PCR.
authors.affiliation: Department of Haematology, Auckland Hospital, and Department of Molecular Medicine, School of Medicine, University of Auckland, Auckland, New Zealand Neil S. Van de Water, B.Sc., Dip.Sc., Ph.D., Scientific Officer, Department of Haematology, Auckland Hospital, and Department of Molecular Medicine, University of Auckland, Private Bag 92 019, Auckland, New Zealand.*Ruth Williams, M.Sc., Research Technician, Department of Molecular Medicine, University of Auckland, Auckland, New Zealand.Elizabeth W. Berry, Q.S.O., M.D., F.R.C.P.A., F.R.A.C.P., Haematologist, Department of Haematology, Auckland Hospital, Auckland, New Zealand.Paul A. Ockelford, M.B.Ch.B., F.R.C.P.A., F.R.A.C.P., Haematologist, Department of Haematology, Auckland Hospital, Auckland, New Zealand.Peter J. Browett, B.Med. Sc., M.B.Ch.B., F.R.C.P.A., F.R.A.C.P., Senior Lecturer in Haematology, Department of Haematology, Auckland Hospital, Auckland, New Zealand.
authors.forename: N S
authors.initials: NS
authors.lastname: VAN DE Water
authors.affiliation: Department of Haematology, Auckland Hospital, and Department of Molecular Medicine, School of Medicine, University of Auckland, Auckland, New Zealand Neil S. Van de Water, B.Sc., Dip.Sc., Ph.D., Scientific Officer, Department of Haematology, Auckland Hospital, and Department of Molecular Medicine, University of Auckland, Private Bag 92 019, Auckland, New Zealand.*Ruth Williams, M.Sc., Research Technician, Department of Molecular Medicine, University of Auckland, Auckland, New Zealand.Elizabeth W. Berry, Q.S.O., M.D., F.R.C.P.A., F.R.A.C.P., Haematologist, Department of Haematology, Auckland Hospital, Auckland, New Zealand.Paul A. Ockelford, M.B.Ch.B., F.R.C.P.A., F.R.A.C.P., Haematologist, Department of Haematology, Auckland Hospital, Auckland, New Zealand.Peter J. Browett, B.Med. Sc., M.B.Ch.B., F.R.C.P.A., F.R.A.C.P., Senior Lecturer in Haematology, Department of Haematology, Auckland Hospital, Auckland, New Zealand.
authors.forename: R
authors.initials: R
authors.lastname: Williams
authors.affiliation: Department of Haematology, Auckland Hospital, and Department of Molecular Medicine, School of Medicine, University of Auckland, Auckland, New Zealand Neil S. Van de Water, B.Sc., Dip.Sc., Ph.D., Scientific Officer, Department of Haematology, Auckland Hospital, and Department of Molecular Medicine, University of Auckland, Private Bag 92 019, Auckland, New Zealand.*Ruth Williams, M.Sc., Research Technician, Department of Molecular Medicine, University of Auckland, Auckland, New Zealand.Elizabeth W. Berry, Q.S.O., M.D., F.R.C.P.A., F.R.A.C.P., Haematologist, Department of Haematology, Auckland Hospital, Auckland, New Zealand.Paul A. Ockelford, M.B.Ch.B., F.R.C.P.A., F.R.A.C.P., Haematologist, Department of Haematology, Auckland Hospital, Auckland, New Zealand.Peter J. Browett, B.Med. Sc., M.B.Ch.B., F.R.C.P.A., F.R.A.C.P., Senior Lecturer in Haematology, Department of Haematology, Auckland Hospital, Auckland, New Zealand.
authors.forename: E W
authors.initials: EW
authors.lastname: Berry
authors.affiliation: Department of Haematology, Auckland Hospital, and Department of Molecular Medicine, School of Medicine, University of Auckland, Auckland, New Zealand Neil S. Van de Water, B.Sc., Dip.Sc., Ph.D., Scientific Officer, Department of Haematology, Auckland Hospital, and Department of Molecular Medicine, University of Auckland, Private Bag 92 019, Auckland, New Zealand.*Ruth Williams, M.Sc., Research Technician, Department of Molecular Medicine, University of Auckland, Auckland, New Zealand.Elizabeth W. Berry, Q.S.O., M.D., F.R.C.P.A., F.R.A.C.P., Haematologist, Department of Haematology, Auckland Hospital, Auckland, New Zealand.Paul A. Ockelford, M.B.Ch.B., F.R.C.P.A., F.R.A.C.P., Haematologist, Department of Haematology, Auckland Hospital, Auckland, New Zealand.Peter J. Browett, B.Med. Sc., M.B.Ch.B., F.R.C.P.A., F.R.A.C.P., Senior Lecturer in Haematology, Department of Haematology, Auckland Hospital, Auckland, New Zealand.
authors.forename: P A
authors.initials: PA
authors.lastname: Ockelford
authors.affiliation: Department of Haematology, Auckland Hospital, and Department of Molecular Medicine, School of Medicine, University of Auckland, Auckland, New Zealand Neil S. Van de Water, B.Sc., Dip.Sc., Ph.D., Scientific Officer, Department of Haematology, Auckland Hospital, and Department of Molecular Medicine, University of Auckland, Private Bag 92 019, Auckland, New Zealand.*Ruth Williams, M.Sc., Research Technician, Department of Molecular Medicine, University of Auckland, Auckland, New Zealand.Elizabeth W. Berry, Q.S.O., M.D., F.R.C.P.A., F.R.A.C.P., Haematologist, Department of Haematology, Auckland Hospital, Auckland, New Zealand.Paul A. Ockelford, M.B.Ch.B., F.R.C.P.A., F.R.A.C.P., Haematologist, Department of Haematology, Auckland Hospital, Auckland, New Zealand.Peter J. Browett, B.Med. Sc., M.B.Ch.B., F.R.C.P.A., F.R.A.C.P., Senior Lecturer in Haematology, Department of Haematology, Auckland Hospital, Auckland, New Zealand.
authors.forename: P J
authors.initials: PJ
authors.lastname: Browett
keywords: DNA diagnosis; factor IX; genetic counselling; haemophilia B; mutation