Background and importance Haemophilia A (HA) is a haemostasis disorder with an incidence of 1:5000 male births and X-linked recessive inheritance. The genetic alteration determines the blood amount of FVIII, which will predict the severity: mild (between 5% and 40%), moderate (1% to 5%) and severe (<1%). Severe haemophilia is present in 60% of haemophiliacs.
Intron 22 and intron 1 inversion represent the main molecular alterations in patients with severe HA (45%–50% and 0.5%–5%).
The development of inhibitors is associated with the treatment and the genetic alteration. 20%–30% of severe HA develop inhibitors. The mutations with the highest incidence of inhibitors are large deletions, with a 42%a–74% prevalence.
Aim and objectives To describe the FVIII gene’s mutation in the haemophilic population in Tenerife and to see the correlation between the genotype and the phenotype of the disease, as well as the influence on the inhibitor’s development.
Material and methods Observational, retrospective and descriptive study. We checked the patient’s clinical history, the mutations and the inhibitor’s record.
Results 44 patients (aged 1, 81 years) were analysed; 21 severe (47.7%), 2 moderate-severe, 4 moderate and 17 mild. The diagnosis was confirmed by molecular biology (polymerase chain reaction (PCR)) in 32 patients (severe and moderate): intron 22 inversion was identified in 14 patients (43.8%), exon 5 substitution in 3 (9.4%), exon 14 insertion in 2 (6.25%), substitution of other exons in 6 (18.75%), small deletions in 4 (12.5%) and exon 4 insertion in 1 (3.12%).
7 patients (15.9%) developed alloantibodies: in 1 patient these are still active and the rest have managed to erase them.
In contrast to the studies performed, the mutations that prevail in the presence of the inhibitor are intron 22 inversions, with an incidence of 71.4%, rather than deletions, with an incidence of 28.6%.
Conclusion and relevance The data on the most prevalent molecular alteration in HA are consistent with those of our patients in Tenerife, since most of them present inversion of intron 22. However, the mutations associated with the development of inhibitors do not coincide with those described in the literature, since most of them are inversions of intron 22.
References and/or acknowledgements 1. Rossetti L. Alteraciones genéticas en hemofilia A. Implicancias en el desarrollo de inhibidores. Advances in Haemophilia 2016;20:180–184.
Conflict of interest No conflict of interest
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