A NOVEL HEMOPHILIA-B DEFECT DUE TO PARTIAL DUPLICATION OF THE FACTOR-IX GENE

A patient with mild FIX deficiency was found to have partial duplicati on of the 3' region of the gene, giving, in addition to the a normal g ene, another piece of DNA containing exons 5', 6', 7' and 8' and the i ntervening sequences. Cloning and sequencing of the junction region re vealed that crossover occurred at nt 31927 in the 3' untranslated regi on of one chromosome/chromatid and nt 10640 in intron 4 of the other. No homology or topoisomerase specific sequences were observed in the c rossover region. PCR and sequencing of illegitimate FIX transcripts fr om the patient's lymphocytes showed at least three different species o f mRNAs. Translation of two of these 'novel' mRNAs should result in tr uncated proteins. Possibilities for the splicing of the mature mRNA ar e offered to explain the translation of a normal-size FM protein, whic h was the only product demonstrated on Western blot analysis.