| Author | Siqueira, Gabriela Queila de Carvalho | |
| Author | Ananina, Galina | |
| Author | Souza, Bruno Batista de | |
| Author | Borges, Murilo Guimarães | |
| Author | Ito, Mirta Tomie | |
| Author | Costa, Sueli Matilde da Silva | |
| Author | Domingos, Igor de Farias | |
| Author | Falcão, Diego Arruda | |
| Author | Cendes, Iscia Lopes | |
| Author | Bezerra, Marcos André Cavalcanti | |
| Author | Araújo, Aderson da Silva | |
| Author | Araújo, Antônio Roberto Lucena | |
| Author | Gonçalves, Marilda de Souza | |
| Author | Saad, Sara Teresinha Olalla | |
| Author | Costa, Fernando Ferreira | |
| Author | Melo, Mônica Barbosa de | |
| Access date | 2019-08-12T16:09:23Z | |
| Available date | 2019-08-12T16:09:23Z | |
| Document date | 2019 | |
| Citation | SIQUEIRA, Gabriela Queila de Carvalho et al. Whole-exome sequencing indicates FLG2 variant associated with leg ulcers in Brazilian sickle cell anemia patients. Experimental Biology and Medicine, v. 244, p. 932–939, 2019. | pt_BR |
| ISSN | 1535-3702 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/34736 | |
| Sponsorship | The São Paulo Research
Foundation [grants 2014/00984–3 and 2015/24029–3]. | pt_BR |
| Language | eng | pt_BR |
| Publisher | SAGE Publications | pt_BR |
| Rights | restricted access | pt_BR |
| Subject in Portuguese | Anemia falciforme | pt_BR |
| Subject in Portuguese | Sequenciamento de todo-exoma | pt_BR |
| Subject in Portuguese | Úlcera de perna | pt_BR |
| Subject in Portuguese | Estudo de associação | pt_BR |
| Subject in Portuguese | Doença complexa | pt_BR |
| Subject in Portuguese | Variantes | pt_BR |
| Title | Whole-exome sequencing indicates FLG2 variant associated with leg ulcers in Brazilian sickle cell anemia patients | pt_BR |
| Type | Article | |
| DOI | 10.1177/1535370219849592 | |
| Abstract | Although sickle cell anemia results from homozygosity for a single mutation at position 7 of the b-globin chain, the clinical aspects of this condition are very heterogeneous. Complications include leg ulcers, which have a negative impact on patients’ quality of life and are related to the severity of the disease. Nevertheless, the complex pathogenesis of this complication has yet to be elucidated. To identify novel genes associated with leg ulcers in sickle cell anemia, we performed whole-exome sequencing of extreme phenotypes in a sample of Brazilian sickle cell anemia patients and validated our findings in another sample. Our discovery cohort consisted of 40 unrelated sickle cell anemia patients selected based on extreme phenotypes: 20 patients without leg ulcers, aged from 40 to 61 years, and 20 with chronic leg ulcers. DNA was extracted from peripheral blood leukocytes and used for whole-exome sequencing. After the bioinformatics analysis, eight variants were selected for validation by Sanger sequencing and TaqManVR genotyping in 293 sickle cell anemia patients (153 without leg ulcers) from two different locations in Brazil. After the validation, Fisher’s
exact test revealed a statistically significant difference in a stop codon variant (rs12568784 G/T) in the FLG2 gene between the GT and GG genotypes (P¼0.035).We highlight the importance of rs12568784 in leg ulcer development as this variant of the FLG2 gene results in impairment of the skin barrier, predisposing the individual to inflammation and infection. Additionally, we suggest that the remaining seven variants and the genes in which they occur could be strong candidates for leg ulcers in sickle cell anemia. | pt_BR |
| Affilliation | University of Campinas. Center for Molecular Biology and Genetic Engineering. Campinas, SP, Brazil. | pt_BR |
| Affilliation | University of Campinas. Center for Molecular Biology and Genetic Engineering. Campinas, SP, Brazil. | pt_BR |
| Affilliation | University of Campinas. Center for Molecular Biology and Genetic Engineering. Campinas, SP, Brazil. | pt_BR |
| Affilliation | University of Campinas. Faculty of Medical Sciences. Department of Medical Genetics and Genome Medicine. Campinas, SP, Brazil. | pt_BR |
| Affilliation | University of Campinas. Center for Molecular Biology and Genetic Engineering. Campinas, SP, Brazil. | pt_BR |
| Affilliation | University of Campinas. Center for Molecular Biology and Genetic Engineering. Campinas, SP, Brazil. | pt_BR |
| Affilliation | Federal University of Pernambuco. Genetics Postgraduate Program. Recife, PE, Brazil. | pt_BR |
| Affilliation | Federal University of Pernambuco. Genetics Postgraduate Program. Recife, PE, Brazil. | pt_BR |
| Affilliation | University of Campinas. Faculty of Medical Sciences. Department of Medical Genetics and Genome Medicine. Campinas, SP, Brazil. | pt_BR |
| Affilliation | Federal University of Pernambuco. Genetics Postgraduate Program. Recife, PE, Brazil. | pt_BR |
| Affilliation | Hematology and Hemotherapy Foundation of Pernambuco, Recife, PE, Brazil. | pt_BR |
| Affilliation | Federal University of Pernambuco. Genetics Postgraduate Program. Recife, PE, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. | pt_BR |
| Affilliation | University of Campinas. Hematology and Hemotherapy Center. Campinas, SP, Brazil. | pt_BR |
| Affilliation | University of Campinas. Hematology and Hemotherapy Center. Campinas, SP, Brazil. | pt_BR |
| Affilliation | University of Campinas. Center for Molecular Biology and Genetic Engineering. Campinas, SP, Brazil. | pt_BR |
| Subject | Sickle cell anemia | pt_BR |
| Subject | Whole-exome sequencing | pt_BR |
| Subject | Leg ulcer | pt_BR |
| Subject | Association study | pt_BR |
| Subject | Complex disease | pt_BR |
| Subject | Variants | pt_BR |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
