Molecular analysis of hemophilia A in Murcia, Spain
Abstract number: PP-MO-536
García Candel1 F., Tizzano2 E., Moreno1 M., Salido1 E., Majado1 M., Moraleda1 J., Funes1 C., Morales1 A.
11Haematology, Hospital Virgen de la Arrixaca, Murcia 22Genetic, Hospital Sant Pau, Barcelona, Spain
How-to-cite García Candel F, Tizzano E, Moreno M, Salido E, Majado M, Moraleda J, Funes C, Morales A. Molecular analysis of hemophilia A in Murcia, Spain. Journal of Thrombosis and Haemostasis 2009; Volume 7, Supplement 2: Abstract PP-MO-536
Introduction: Haemophilia A is an X-linked, recessively inherited bleeding disorder which results from deficiency of procoagulant factor VIII (FVIII). Molecular genetics is a critical tool for prenatal diagnosis and to identify the carrier state. The FVIII gene intron 22 inversion mutation is the cause of Haemophilia A in 20% of patients and always produces severe disease (causative mutation in approximately 45% of severe haemophilia A). Our aim was to identify the molecular genetic alterations in the Haemophilia patients diagnosed in Murcia, Spain, and to compare our results with The Haemophilia A Mutation, Structure, Test and Resource Site (HAMSTeRS).
Methods: We studied 49 patients with haemophilia A (21 severe, 7 moderate and 21 mild) distributed in 29 families (19 severe, 3 moderate, 7 mild). The DNA was extracted from whole blood (10 mL). Afterwards we performed a direct sequencing of the gene of FVIII by polymerase chain reaction (PCR). We compare the results of our patients with the database HAMSTeRS.
Results: Ten families with FVIII gene intron 22 inversion, 16 families with point mutations (5 with missense mutation in exon 7 -one was not mentioned in HAMSTeRS-, two with missense mutation in exon 20, one with missense mutation in exon 3 -not mentionated in HAMSTeRS-, one with missense mutation in exon 4 -not mentionated in HAMSTeRS-, one with missense mutation in exon 8, one with missense mutation in exon 11, one with missense mutation in exon 12, one with nonsense mutation in exon 14, one with nonsense mutation in exon 18, one with missense mutation in exon 23 -not mentionated in HAMSTeRS- and one family with splicing mutation). We found one family with a frameshift large deletion (exons 23–26 affected) and three families with frameshift small deletion (two families with exon 14 affected and one family with exon 26 affected).
Conclusions: FVIII gene intron 22 inversion was the most frequent genetic aberration in our series. Point mutations involved preferentially exon 7. We have identified four new mutations not previously reported to HAMSTeRS. These data emphasize the importance of performing genetic studies in the families with Haemophilia A for an appropriate genetic counselling and correct prenatal diagnosis.
Disclosure of interest: none declared.