Hemophilia Research Today is a free monthly online journal that collates and summarizes the latest research about Hemophilia, including details on genetics, causes, symptoms, blood transfusion.

Mutation analysis in 51 patients with haemophilia A: report of 10 novel mutations and correlations between genotype and clinical phenotype.

Hill M, Deam S, Gordon B, Dolan G

Department of Clinical Chemistry and Haematology, University Hospital, Queens Medical Centre, Nottingham, UK. marian.hill@nottingham.ac.uk

We report the results of genetic analysis on a series of 51 patients attending this Haemophilia Comprehensive Care Centre. The most common cause of severe haemophilia A--the factor VIII intron 22 inversion was detected in eight families and the factor VIII intron 1 inversion in three families. Mutation analysis was carried out on the remaining patients by nucleotide sequencing of genomic DNA after screening with conformation-sensitive gel electrophoresis (CSGE) or denaturing high-performance liquid chromatography (dHPLC). A total of 27 different FVIII non-inversion mutations were detected. Severe haemophilia was associated with 12 null mutations (six nonsense, six frameshift) and four missense mutations. A further 11 different missense mutations were associated with moderate or mild disease. To our knowledge, six null mutations [1950del 4(tttg), 3270-75insA, 4416del 10, 6735-38delA, W1029X, Y1792X] and four missense mutations (E1682K, M1947V, P2048L, P2143L) have not been previously published. Each novel missense mutation occurred at a highly conserved residue, no other candidate mutation was detected on screening the entire coding region of the FVIII gene and they were not detected in a screen of individuals without haemophilia A. The genotype-phenotype correlations of the FVIII mutations detected will be discussed.

Published 6 April 2005 in Haemophilia, 11(2): 133-41.
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