Haemophilia A: database of ncleotide substituttions, deletions, insertions and rearrangements of the factor VIII gene

作者：Edward G. D. Tuddenham, D.N. Cooper, Jane Gitschier, Miyoko Higuchi, Leon W. Hoyer, Akira Yoshioka, I. R. Peake, R. Schwaab, K. Olek, H H Kazazian, J. Maurice Lavergne, Francesco Giannelli, Stylianos E. Antonarakis · 发表于：Nucleic Acids Research · 年份：1991 · DOI：10.1093/nar/19.18.4821 · 被引用次数：122 · 研究领域：Hemophilia Treatment and Research、Cancer-related gene regulation、Blood Coagulation and Thrombosis Mechanisms

Mutations at the factor VIII gene locus causing Haemophilia A have now been identified in many patients from many ethnic groups. Earlier studies used biased methods which detected repetitive mutations at a few CG dinucleotides. More recently rapid gene scanning methods have uncovered an extreme diversity of mutations. Over 80 different point mutations, 6 insertions, 7 small deletions, and 60 large deletions have been characterised. Repetitive mutation has been proved for at least 16 CpG sites. All nonsense mutations cause severe disease. Most missense mutations appear to cause instability of the protein, but some are associated with production of dysfunctional factor VIII molecules, thereby localising functionally critical regions of the cofactor. Variable phenotype has been observed in association with three of the latter class of genotype. This catalogue of gene lesions in Haemophilia A will be updated annually.