Two families from Argentina with factor X deficiency due two different mutations (p.Cys241Gly and p.Gln138Arg)

Toronto

Congreso; XXV Congress of the International Society on Thrombosis and Haemostasis; 2015

ISTH

Background: Coagulation factor X (FX) deficiency is a rare autosomal recessive disease and is one of the most severe among inherited rare bleeding disease. Very few cases of congenital FX deficiency have been reported from South America. Aims: We have detected two unrelated families from the Cordoba area in the centre of Argentina whose members presented two new mutations. Subjects and methods: Family A (GM): The proposita is a 41 year old female who has had all her life a moderate bleeding tendency . Parents were not consanguineous and their background was Spanish ?Argentinean. Family B (FD): The proposita was a 51 year old female who had a mild bleeding tendency. Parents were not consanguineous and had an Italian-Argentinian background. Prothrombin time (PT), Russell´s viper venom clotting time (RVV) and aPTT were assayed using standard techniques. FX activity was determined using a one-stage clotting assay based upon PT, and FX chromogenic level was measured using commercial kit (Hyphen BioMed, France). Coding regions and exon/intron boundaries of FX were amplified in DNA samples by PCR and the products obtained were sequenced. Results: The proposita GM showed a prolongation of aPTT, PT and RVV. There was no circulating anticoagulant. The FX clotting activity level was 3% of normal and chromogenic of 0.04 IU/ml. Genetic analysis showed a p.Cys241Gly mutation in exon 6. Other family members presented the same mutation. The patient FD the aPTT, PT, and RVV were prolonged and the FX clotting activity was 2% of normal and chromogenic 0.03 IU/ML. Again there was no circulating anticoagulant. Genetic analysis revealed the presence of a p.Gln138Arg mutation in exon 5. Other family members showed the same mutation. Discusion: These are the first FX mutations reported in Argentina. Extensive family studies are underway in order to define the diffusion of these two defects in the local population. Since the two mutations have never been describes in Spain or Italy or in any other part of the world, it is plausible that the founder was Argentinean.