Two novel point mutations correlate with an altered developmental expression of blood coagulation factor IX (hemophilia B Leyden phenotype)

Abstract

Hemophilia B Leyden is characterized by low levels of factor IX antigen and activity before the age of 15 years, whereas after puberty factor IX levels rise at a rate of about 5% per year. Two distinct point mutations (deletion of A, A----G) were identified at position +13 of the factor IX gene of a Greek and an American patient with hemophilia B Leyden. The nucleotide changes have occurred 32 basepairs downstream of a previously reported point mutation in a Dutch kindred with the same hemophilic phenotype. The results point to the importance of sequences surrounding the putative start site for the constitutive expression of the factor IX gene and to the possible significance of an imperfect direct repeat of DNA.