Abstract:
Hemophilia B, the third common hereditary coagulopathy, is very heterogeneous at both phenotypic and genotypic levels. This X-linked recessive disease is caused by the production of either reduced amounts or functionally defective forms of the coagulation factor IX. In order to undertake a comprehensive molecular analysis of the FIX gene in the Turkish population 41 hemophilia B patients were screened for mutations by ddF and direct DNA sequencing to contribute to the knowledge of genotype-phenotype correlations in hemophilia B and to construct a Turkish mutation profile. A hypervariable polymorphic site within the FIX gene have also been analyzed. Thirty-two mutations were identified in Turkish hemophilia B patients, including 4 novel single base changes and 2 novel gross rearrangements. The mutation profile of the Turkish population was found to be similar to the general profile observed worldwide. Haplotype analysis revealed the independent origin of 4 recurrent mutations. All patient data was compiled in a national database, which efficiently shows the mutation/phenotype/haplotype relations. The analysis of the hypervariable region in intron 1 in 85 Turkish individuals revealed the presence of a novel allele and showed that the Turkish population carries the Caucasian specific allele as the most frequent one.
