A recurrent missense mutation (Arg → Gln) and a partial deletion in factor VIII gene causing severe haemophilia A

Summary The presence of gene lesions in coagulation factor VIII (FVIII) gene was investigated in 70 Italian patients severely affected by haemophilia A. cDNA probes specific for exons 14–26 of the FVIII gene were used. In two related patients a gene deletion removes exon 26, a gene lesion similar to that described previously in a British haemophiliac. In exon 24 a C to T transition in the reverse complement strand causes a missense mutation in the coding strand (CGA CAA, 2209 Arg Gln). The mutation is located in a very conserved FVIII homology region and severely reduces FVIII activity. By restriction analysis and hybridizations with oligonucleotide probes this gene alteration was found in two unrelated haemophiliacs and in their relatives.