Start of UK Confidential Haemophilia A Database: Analysis of 142 Patients by Solid Phase Fluorescent Chemical Cleavage of Mismatch

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Abstract
A national strategy for optimising genetic services in haemophilia A has been initiated in the UK. Solid phase fluorescent chemical cleavage of mismatch is used to screen the entire coding region of factor VIII in six segments: four amplified from the trace of mRNA in blood lymphocytes and two from genomic DNA for the 3.4 kb exon 14 and flanking intron sequences. These segments are analysed in two threefold multiplexes so that the genes of 18 patients can be screened in a single ABI 377 gel. The promoter and polyadenylation signal region are amplified and sequenced directly. We have analysed 142 unrelated patients and identified 141 factor VIII mutations and one Normandy type von Willebrand homozygote. The former mutations include 89 missense, 10 nonsense, 5 frameshift, one 24 bp deletion and one splice signal defect. These comprise 71 different changes, of which 39 have not been previously observed. * Professor Christine Lee, Haemophilia Centre, The Royal Free Hospital, London; Dr. B. T. Colvin, Department of Haematology, The Royal London Hospital, London; Dr. M. Wassef, Dr. A. Milne, North Hampshire Haemophilia Centre, Holybourne, Alton, Hants; Dr. P. Collins, The Arthur Bloom Centre, Department of Haematology, University Hospital of Wales, Cardiff; Dr. P. Giangrande, Oxford Haemophilia Centre, Churchill Hospital, Headington, Oxford; Dr. T. Baglin, Clinical Haematology, Addenbrooke's Hospital, Cambridge; Dr. M. Winter, Haemophilia Centre, Kent and Canterbury Hospital, Canterbury; Dr. P. Bolton-Maggs, Alder Hey Children's Hospital, Liverpool; Dr. D. G. Oscier, Bournemouth Haemophilia Centre, Royal Bournemouth Hospital, Bournemouth; Dr. G. D. O. Lowe, University Department of Medicine, Royal Infirmary, Glasgow; Dr. S. V. Davies, Haematology Laboratory, Yeovil District Hospital, Yeovil; Dr. S. A. Fairham, Peterborough District Hospital, Peterborough; Dr. H. E. T. Korn, Haemophilia Centre, Ysbyty Gwynedd, Bangor, Gwynedd; Dr. G. L. Scott, Department of Haematology, Bristol Royal Infirmary, Bristol; Dr. J. P. L. A. Hayes, Department of Haematology, All Saints Hospital, Chatham; Dr. B. Gibson, Department of Haematology, Royal Hospital for Sick Children, Yorkhill, Glasgow; Dr. B. A. McVerry, Haemophilia Unit, St James University Hospital, Leeds; Dr. C. H. Toh, Haematology Laboratories, Royal Liverpool University Hospital, Liverpool; Dr. M. Chisholm, Southampton General Hospital, Southampton, UK