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Keywords:

  • FVIII;
  • mutation;
  • molecular pathology

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-clamped primers. The GC-clamped PCR products were screened by denaturing gradient gel electrophoresis (DGGE) and fragments showing an abnormal migration pattern were sequenced. 17 mutations were identified, of which four were splicing defects, involving the first 1–6 nucleotide (nt) in the intervening sequences (IVS), six missense mutations, three nonsense mutations and four frameshift mutations. 14 other patients carried the type 1 inversion, affecting the distal copy of the F8A gene at the telomere of the X chromosome and the same gene in intron 22 of the FVIII gene. All the mothers studied (12/14) were carriers of the inversion. Two of these patients with inversion also have a co-existing missense mutation. In most cases the clinical severity of the disease corresponds to the genotype.