Genetic Characterization of the Factor VIII Gene in a Cohort of Colombian Patients with Severe Hemophilia A with Inhibitors

• Published in: Hematology reports Vol. 14; no. 2; pp. 149 - 154
• Main Authors: Doncel, Samuel Sarmiento, Mosquera, Gina Alejandra Diaz, Pelaez, Ronald Guillermo, Cortes, Javier Mauricio, Rico, Carol Agudelo, Cadavid, Francisco Javier Meza, Plazas, Nelson Ramirez, Amar, Ivan Alfredo Perdomo, Siado, Jorge Enrique Peña, Rey, Fabian Andres Parrado, Montaño, Cesar Alberto, Villadiego, Alexys Maza
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 04.05.2022; MDPI
• Subjects: Brief Report; Coagulation factors; Disease prevention; factor VIII; Gene deletion; Genetic analysis; Genetic factors; Hemophilia; hemophilia A; Hemostasis; inhibitor; Inversion; Medical records; Mutation; Nonsense mutation; Prophylaxis; Risk factors; X chromosome; Colombia; hemophilia A; mutation; inhibitor; factor VIII; X chromosome
• ISSN: 2038-8322; 2038-8330; 2038-8330
• DOI: 10.3390/hematolrep14020022

Hemophilia A is an X-linked bleeding disorder caused by mutations in the FVIII gene. Genetic factors have been shown to be a risk factor for the development of inhibitors. We aimed to identify the specific variations of the FVIII gene of patients with hemophilia A with inhibitors and their association with the inhibitor titer. Methods: Cross-sectional descriptive study. We included 12 Colombian patients from a health care provider, "Integral Solutions SD", who underwent analysis of genetic material (DNA), which was reported by the Molecular Hemostasis Laboratory in Bonn, Germany. Results: All of these patients were diagnosed with severe hemophilia A with inhibitors; ages ranged between 6 and 48 years, with a median age of 13.5 years. Molecular analysis showed the inversion of intron 22 in six patients (50.0%), a small duplication in two patients (16.7%), the inversion of intron 1 in one patient (8.3%), a large deletion (8.3%), a nonsense mutation (8.3%) and a splice-site (8.3%), findings similar to those of other studies. A total of 58.3% of the patients presented inversion mutations with a high risk of developing inhibitors A total of 83.3% of the evaluated patients presented null mutations; however the presence of high inhibitor titers was 66.7%. The most frequent mutation was the inversion intron 22. Knowing the type of mutation and its association as a risk factor for generating inhibitors invites us to delve into other outcomes such as residual values of coagulation FVIII as well as its impact on the half-life of the exogenous factor applied in prophylaxis.