Genetic Characterization of the Factor VIII Gene in a Cohort of Colombian Patients with Severe Hemophilia A with Inhibitors
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 associati...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Hematology Reports |
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| Online Access: | https://www.mdpi.com/2038-8330/14/2/22 |
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| author | Samuel Sarmiento Doncel Gina Alejandra Diaz Mosquera Ronald Guillermo Pelaez Javier Mauricio Cortes Carol Agudelo Rico Francisco Javier Meza Cadavid Nelson Ramirez Plazas Ivan Alfredo Perdomo Amar Jorge Enrique Peña Siado Fabian Andres Parrado Rey Cesar Alberto Montaño Alexys Maza Villadiego |
| author_facet | Samuel Sarmiento Doncel Gina Alejandra Diaz Mosquera Ronald Guillermo Pelaez Javier Mauricio Cortes Carol Agudelo Rico Francisco Javier Meza Cadavid Nelson Ramirez Plazas Ivan Alfredo Perdomo Amar Jorge Enrique Peña Siado Fabian Andres Parrado Rey Cesar Alberto Montaño Alexys Maza Villadiego |
| author_sort | Samuel Sarmiento Doncel |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T23:39:37Z |
| format | Article |
| id | doaj.art-14a11c42b05446b39221c90d304c6f1b |
| institution | Directory Open Access Journal |
| issn | 2038-8330 |
| language | English |
| last_indexed | 2024-03-09T23:39:37Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Hematology Reports |
| spelling | doaj.art-14a11c42b05446b39221c90d304c6f1b2023-11-23T16:54:01ZengMDPI AGHematology Reports2038-83302022-05-0114214915410.3390/hematolrep14020022Genetic Characterization of the Factor VIII Gene in a Cohort of Colombian Patients with Severe Hemophilia A with InhibitorsSamuel Sarmiento Doncel0Gina Alejandra Diaz Mosquera1Ronald Guillermo Pelaez2Javier Mauricio Cortes3Carol Agudelo Rico4Francisco Javier Meza Cadavid5Nelson Ramirez Plazas6Ivan Alfredo Perdomo Amar7Jorge Enrique Peña Siado8Fabian Andres Parrado Rey9Cesar Alberto Montaño10Alexys Maza Villadiego11Integral Solutions SD SAS, Integral Solutions Research, Bogota 110121, ColombiaIntegral Solutions SD SAS, Integral Solutions Research, Bogota 110121, ColombiaLife Sciences and Health Research Group, Graduates School, CES University, Medellin 050021, ColombiaIntegral Solutions SD SAS, Integral Solutions Research, Bogota 110121, ColombiaIntegral Solutions SD SAS, Integral Solutions Research, Bogota 110121, ColombiaIntegral Solutions SD SAS, Integral Solutions Research, Bogota 110121, ColombiaIntegral Solutions SD SAS, Integral Solutions Research, Bogota 110121, ColombiaIntegral Solutions SD SAS, Integral Solutions Research, Bogota 110121, ColombiaIntegral Solutions SD SAS, Integral Solutions Research, Bogota 110121, ColombiaIntegral Solutions SD SAS, Integral Solutions Research, Bogota 110121, ColombiaIntegral Solutions SD SAS, Integral Solutions Research, Bogota 110121, ColombiaIntegral Solutions SD SAS, Integral Solutions Research, Bogota 110121, ColombiaHemophilia 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.https://www.mdpi.com/2038-8330/14/2/22factor VIIIhemophilia AinhibitormutationX chromosome |
| spellingShingle | Samuel Sarmiento Doncel Gina Alejandra Diaz Mosquera Ronald Guillermo Pelaez Javier Mauricio Cortes Carol Agudelo Rico Francisco Javier Meza Cadavid Nelson Ramirez Plazas Ivan Alfredo Perdomo Amar Jorge Enrique Peña Siado Fabian Andres Parrado Rey Cesar Alberto Montaño Alexys Maza Villadiego Genetic Characterization of the Factor VIII Gene in a Cohort of Colombian Patients with Severe Hemophilia A with Inhibitors Hematology Reports factor VIII hemophilia A inhibitor mutation X chromosome |
| title | Genetic Characterization of the Factor VIII Gene in a Cohort of Colombian Patients with Severe Hemophilia A with Inhibitors |
| title_full | Genetic Characterization of the Factor VIII Gene in a Cohort of Colombian Patients with Severe Hemophilia A with Inhibitors |
| title_fullStr | Genetic Characterization of the Factor VIII Gene in a Cohort of Colombian Patients with Severe Hemophilia A with Inhibitors |
| title_full_unstemmed | Genetic Characterization of the Factor VIII Gene in a Cohort of Colombian Patients with Severe Hemophilia A with Inhibitors |
| title_short | Genetic Characterization of the Factor VIII Gene in a Cohort of Colombian Patients with Severe Hemophilia A with Inhibitors |
| title_sort | genetic characterization of the factor viii gene in a cohort of colombian patients with severe hemophilia a with inhibitors |
| topic | factor VIII hemophilia A inhibitor mutation X chromosome |
| url | https://www.mdpi.com/2038-8330/14/2/22 |
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