| Author | Abreu, Gabriella de Medeiros | |
| Author | Soares, Camila de Almeida Pereira Dias | |
| Author | Tarantino, Roberta Magalhães | |
| Author | Fonseca, Ana Carolina Proença da | |
| Author | Souza, Ritiele Bastos de | |
| Author | Pereira, Maria de Fátima Carvalho | |
| Author | Cabello, Pedro Hernan | |
| Author | Rodacki, Melanie | |
| Author | Zajdenverg, Lenita | |
| Author | Zembrzuski, Verônica Marques | |
| Author | Campos Junior, Mário | |
| Access date | 2020-12-11T19:25:05Z | |
| Available date | 2020-12-11T19:25:05Z | |
| Document date | 2020 | |
| Citation | ABREU, Gabriella de Medeiros et al. Identification of the First PAX4-MODY family reported in Brazil. Diabetes, Syndrome and Obesity: Targets and Therapy, v. 13, p. 2623-2631, 2020. | pt_BR |
| ISSN | 1178-7007 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/44855 | |
| Language | eng | pt_BR |
| Publisher | Dovepress | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Diabetes mellitus | pt_BR |
| Subject in Portuguese | Diabetes monogênica | pt_BR |
| Subject in Portuguese | PAX4 | pt_BR |
| Subject in Portuguese | MODY | pt_BR |
| Subject in Portuguese | Mutação | pt_BR |
| Title | Identification of the First PAX4-MODY Family Reported in Brazil | pt_BR |
| Type | Article | |
| DOI | 10.2147/DMSO.S256858 | |
| Abstract | Purpose: The aim of this study was to sequence the coding region of the PAX4 gene in a Brazilian cohort with clinical manifestations of monogenic diabetes. Patients and Methods: This study included 31 patients with autosomal dominant history of diabetes, age at diagnosis ≤ 40 years, BMI < 30 kg/m2, and no mutations in GCK or HNF1A, HNF4A, and HNF1B. Screening of the PAX4 coding region was performed by Sanger sequencing. In silico algorithms were used to assess the potential impact of amino acid substitutions on protein structure and function. Additionally, PAX4-MODY family members and 158 control subjects without diabetes were analyzed for the identified mutation. Results: The molecular analysis of PAX4 has detected one missense mutation, p.Arg164Gln (c.491G>A), segregating with diabetes in a large Brazilian family. The mutation was absent among the control group. The index case is a woman diagnosed at 32 years of age with polyneuropathy and treated with insulin. She did not present diabetic renal disease or retinopathy. Family members with the PAX4 p.Arg164Gln mutation have a heterogeneous clinical manifestation and treatment response, with age at diagnosis ranging from 24 years to 50 years. Conclusion: To the best of our knowledge, this is the first study to report a PAX4-MODY family in Brazil. The age of PAX4-MODY diagnosis in the Brazilian family seems to be higher than the classical criteria for MODY. Our results reinforce the importance of screening large monogenic diabetes families for the understanding of the clinical manifestations of rare forms of diabetes for the specific and personalized treatment. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Departamento de Medicina Interna. Seção de Diabetes e Nutrologia. Rio de Janeiro, RJ, Brasil / Instituto Estadual de Diabetes e Endocrinologia Luiz Caproglione. Ambulatório de Diabetes. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Departamento de Patologia Clínica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil / Universidade do Grande Rio. Escola de Ciência da Saúde. Laboratório de Genética. Rio de Janeiro, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Departamento de Medicina Interna. Seção de Diabetes e Nutrologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Rio de Janeiro. Departamento de Medicina Interna. Seção de Diabetes e Nutrologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil | pt_BR |
| Subject | Diabetes mellitus | pt_BR |
| Subject | Monogenic diabetes | pt_BR |
| Subject | PAX4 | pt_BR |
| Subject | MODY | pt_BR |
| Subject | Mutation | pt_BR |
