Identification of de novo deletion in the factor VIII gene by ...

Blood coagulation evaluation performed preoperatively in two unrelated girls with isolated prolongation of the activated partial thromboplastin time (APTT) and no family history of bleeding disorder revealed a mild factor VIII deficiency. Quantitative and qualitative defect of von Willebrand factor was not present. Genetic analysis of the F8 gene identified no mutations. In contrast, quantitative gene screening using multiplex ligation dependent probe amplification (MLPA) revealed a large heterozygous deletion of the F8 gene in both patients consistent with a carrier status of sporadic severe haemophilia A. This report illustrates that MLPA technique represents an efficient method to screen for large F8 gene deletions in sporadic undiagnosed carriers of haemophilia A.