Identification of a novel mutation in the factor VIII gene causing severe haemophilia A

Deficiency in coagulation factor VIII encoded by results in the X-linked recessive bleeding disorder haemophilia A (HEMA). Here we describe the identification of a novel variant in the factor VIII gene, , in an adult male patient with severe haemophilia A. The patient was diagnosed in early childhood and subsequently co-infected with Hepatitis C and HIV acquired during early blood transfusion for haemophilia in the 1980ies. The identified deletion, c.5411_5413delTCT, p.F1804del lies within a conserved part of the molecule, is predicted by bioinformatic software to be deleterious by the loss of Phenylalanine, and has not been previously described in any database. This novel deletion as a cause of haemophilia A did not result in generation of inhibitory antibodies to Factor VIII treatment and may have impact on (prenatal) diagnosis, genetic counselling, and treatment decisions in the affected family as well as in other families diagnosed with this mutation. Finally, this novel mutation should be included in the panel of known genetic variants in when searching for the genetic etiology in patients suspected of HEMA.