Sequenciamento genético em pacientes com sobrecarga de ferro primária
Data
2023-06-05
Autores
Alvarenga, Aline Morgan 
Orientadores
Santos, Paulo Caleb Júnior de Lima
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
A hemocromatose é uma doença autossômica recessiva, causada por uma diminuição na
concentração de hepcidina ou uma redução na ligação entre hepcidina e ferroportina. A
principal variante genética associada à hemocromatose é a p.Cys282Tyr em homozigose
no gene HFE. Outras variantes nos genes HJV, HAMP, TFR2, SLC40A1, BMP6 e FTL
também têm sido associadas à sobrecarga de ferro. Este projeto possui dois objetivos,
sendo o primeiro deles efetuar o sequenciamento, através de metodologia de Sanger, nos
éxons dos genes citados, em amostras de pacientes com sobrecarga de ferro cujas causas
secundárias foram excluídas e não possuem a variante p.Cys282Tyr em homozigose no
gene HFE. O segundo objetivo foi realizar divulgação científica sobre hemocromatose
através do Grupo Brasileiro de Hemocromatose (GBH). O sequenciamento dos genes
BMP6 e FTL foi realizado e após a análise foram encontradas duas variantes patogênicas
e uma variante de significado incerto (VUS) no gene BMP6, sendo que duas delas não
foram descritas em literatura. Estes resultados renderam a publicação de um artigo
científico. Para o gene FTL foi encontrada uma variante patogênica já descrita e a partir
deste resultado foi publicado um case report. O gene HFE foi sequenciado em todos os
pacientes, mas não foram obtidos resultados concretos, e devido à falta de financiamento
não foi possível sequenciar os demais genes (HJV, HAMP, TFR2 e SLC40A). Além dos
artigos citados, também foi publicada uma revisão a respeito da hemocromatose e um
trabalho sobre qualidade de vida em pacientes com hemocromatose. A identificação de
variantes patogênicas no gene BMP6 e FTL podem contribuir para a compreensão
genética da sobrecarga de ferro e projetos no modelo do GBH são de extrema importância
para a educação em saúde, contribuindo para a democratização da informação, prevenção
da doença e qualidade de vida.
Hemochromatosis is an autosomal recessive disease, caused by a decrease in hepcidin concentration or reduction of a binding between hepcidin and ferroportin. The main genetic variant associated with hemochromatosis is the homozygous p.Cys282Tyr in the HFE gene. Other variants in the HJV, HAMP, TFR2, SLC40A1, BMP6 and FTL genes have also been associated with iron overload. This project has two objectives, the first of which is controlled sequencing, through Sanger's methodology, in the exons of the mentioned genes, in the selection of patients with iron overload whose secondary causes have been excluded and who do not have a homozygous p.Cys282Tyr variant in the HFE gene. The second objective was to carry out scientific dissemination on hemochromatosis through the Brazilian Group of Hemochromatosis (GBH). The sequencing of the BMP6 and FTL genes was carried out and after the analysis, two pathogenic variants and a variant of uncertain significance (VUS) were found in the BMP6 gene, two of which have not been described in the literature. These results resulted in the publication of a scientific article. For the FTL gene, a previously described pathogenic variant was found and based on this result, a case report was published. The HFE gene was sequenced in all patients, but no concrete results were obtained, and due to lack of funding it was not possible to sequence the other genes (HJV, HAMP, TFR2 and SLC40A). In addition to the cited articles, a review on hemochromatosis and a study on quality of life in patients with hemochromatosis was also published. The identification of pathogenic variants in the BMP6 and gene can contribute to the genetic understanding of iron overload and projects in the GBH model are of extreme importance for health education, confident for the democratization of information, disease prevention and quality of life.
Hemochromatosis is an autosomal recessive disease, caused by a decrease in hepcidin concentration or reduction of a binding between hepcidin and ferroportin. The main genetic variant associated with hemochromatosis is the homozygous p.Cys282Tyr in the HFE gene. Other variants in the HJV, HAMP, TFR2, SLC40A1, BMP6 and FTL genes have also been associated with iron overload. This project has two objectives, the first of which is controlled sequencing, through Sanger's methodology, in the exons of the mentioned genes, in the selection of patients with iron overload whose secondary causes have been excluded and who do not have a homozygous p.Cys282Tyr variant in the HFE gene. The second objective was to carry out scientific dissemination on hemochromatosis through the Brazilian Group of Hemochromatosis (GBH). The sequencing of the BMP6 and FTL genes was carried out and after the analysis, two pathogenic variants and a variant of uncertain significance (VUS) were found in the BMP6 gene, two of which have not been described in the literature. These results resulted in the publication of a scientific article. For the FTL gene, a previously described pathogenic variant was found and based on this result, a case report was published. The HFE gene was sequenced in all patients, but no concrete results were obtained, and due to lack of funding it was not possible to sequence the other genes (HJV, HAMP, TFR2 and SLC40A). In addition to the cited articles, a review on hemochromatosis and a study on quality of life in patients with hemochromatosis was also published. The identification of pathogenic variants in the BMP6 and gene can contribute to the genetic understanding of iron overload and projects in the GBH model are of extreme importance for health education, confident for the democratization of information, disease prevention and quality of life.