MOLECULAR CHARACTERIZATION OF HEMOPHILIA-A IN SOUTHERN CHINESE

41 unrelated southern Chinese haemophilia A patients were studied, The 5' promoter region, all 26 exons, their immediate 5' and 3' flanking splice junctions and the 3' untranslated region of the FVIII gene were amplified (including 16 different segments of exon 14) using GC-clamp ed primers. The CC-clamped PCR products were screened by denaturing gr adient gel electrophoresis (DGGE) and fragments showing an abnormal mi gration pattern were sequenced, 17 mutations were identified, of which four were splicing defects, involving the first 1-6 nucleotide (nt) i n the intervening sequences (IVS), six missense mutations, three nonse nse mutations and four frameshift mutations. 14 other patients carried the type 1 inversion, affecting the distal copy of the F8A gene at th e telomere of the X chromosome and the same gene in intron 22 of the F VIII gene. All the mothers studied (12/14) were carriers of the invers ion. Two of these patients with inversion also have a co-existing miss ense mutation. In most cases the clinical severity of the disease corr esponds to the genotype.