Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity

Detalhes bibliográficos
Autor(a) principal: Salum, Kaio Cezar Rodrigues
Data de Publicação: 2020
Outros Autores: Souza, Guilherme Orofino de, Abreu, Gabriella de Medeiros, Campos Junior, Mário, Kohlrausch, Fabiana Barzotto, Carneiro, João Regis Ivar, Nogueira Neto, José Firmino, Magno, Fernanda Cristina C. Mattos, Rosado, Eliane Lopes, Palhinha, Lohanna, Monteiro, Clarissa Menezes Maya, Csbello, Giselda Maria Kalil de, Csbello, Pedro Hernán, Bozza, Patrícia Torres, Zembrzuski, Verônica Marques, Fonseca, Ana Carolina Proença da
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/45040
Resumo: Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Geral. Laboratório de Genética Humana. Niterói, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil.
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spelling Salum, Kaio Cezar RodriguesSouza, Guilherme Orofino deAbreu, Gabriella de MedeirosCampos Junior, MárioKohlrausch, Fabiana BarzottoCarneiro, João Regis IvarNogueira Neto, José FirminoMagno, Fernanda Cristina C. MattosRosado, Eliane LopesPalhinha, LohannaMonteiro, Clarissa Menezes MayaCsbello, Giselda Maria Kalil deCsbello, Pedro HernánBozza, Patrícia TorresZembrzuski, Verônica MarquesFonseca, Ana Carolina Proença da2020-12-18T13:47:16Z2020-12-18T13:47:16Z2020SALUM, Kaio Cezar Rodrigues et al. Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity. Frontiers in Genetics, v. 11, Article 608840, p. 1-10, Dec. 2020.1664-8021https://www.arca.fiocruz.br/handle/icict/4504010.3389/fgene.2020.608840engFrontiers MediaObesidade severaMC4RObesidade monogênica não sindrômicaInício da idade adultaMutaçãoSevere obesityMC4RNon-syndromic monogenic obesityAdulthood-onsetMutationIdentification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesityinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Geral. Laboratório de Genética Humana. Niterói, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Geral. Laboratório de Genética Humana. Niterói, RJ, Brasil.Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Departamento e Laboratório de Patologia. Rio de Janeiro. RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Nutrição Josué de Castro. Rio de Janeiro. RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Nutrição Josué de Castro. Rio de Janeiro. RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil / Universidade Grande Rio. Laboratório de Genética Humana. Rio de Janeiro. RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Background: The melanocortinergic pathway orchestrates the energy homeostasis and impairments in this system often lead to an increase in body weight. Rare variants in the melanocortin 4 receptor (MC4R) gene resulting in partial or complete loss of function have been described with autosomal co-dominant inheritance. These mutations are the most common cause of non-syndromic monogenic obesity. In this context, this study aimed to sequence the MC4R gene in a Brazilian cohort of adults with severe obesity. Methods: This study included 163 unrelated probands with Body Mass Index (BMI) ≥ 35 kg/m2, stratified into three groups, according to the period of obesity onset. From the total sample, 25 patients were enrolled in the childhood-onset group (0–11 years), 19 patients in the adolescence/youth-onset group (12–21 years), and 119 patients in the adult-onset group (>21 years). Blood pressure, anthropometric and biochemical characteristics were obtained, and the MC4R coding region of each subject’s DNA was assessed using automated Sanger sequencing. Results: Significant anthropometric differences between the groups were observed. Higher body weight and BMI medians were found in patients with childhood-onset or adolescence/youth-onset when compared to the adulthood-onset obesity group. A total of five mutations were identified, including four missense variants: p.Ser36Thr, p.Val103Ile, p.Ala175Thr, and p.Ile251Leu. Additionally, we observed one synonymous variant (p.Ile198=). The p.Ala175Thr variant was identified in a female case with severe obesity and adulthood-onset. This variant was previously described as a partial loss-offunction mutation, in which the minor allele poses dominant-negative effect, probably resulting in reduced cAMP activity. Conclusion: This study showed a prevalence of common and rare variants in a cohort of Brazilian adults with severe obesity and candidates to bariatric surgery. We have identified a rare potentially pathogenic MC4R variant in a Brazilian patient with severe and adulthood-onset obesity.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/45040/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALCaioCesarSalum_PedroCebello_etal_IOC_2020.pdfCaioCesarSalum_PedroCebello_etal_IOC_2020.pdfapplication/pdf1214277https://www.arca.fiocruz.br/bitstream/icict/45040/2/CaioCesarSalum_PedroCebello_etal_IOC_2020.pdfb8f73ca891b189f6dcbd9ab21db3342dMD52TEXTCaioCesarSalum_PedroCebello_etal_IOC_2020.pdf.txtCaioCesarSalum_PedroCebello_etal_IOC_2020.pdf.txtExtracted texttext/plain51085https://www.arca.fiocruz.br/bitstream/icict/45040/3/CaioCesarSalum_PedroCebello_etal_IOC_2020.pdf.txtc6902f78db43e92f775d484fcc95d784MD53icict/450402021-03-13 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dc.title.pt_BR.fl_str_mv Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity
title Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity
spellingShingle Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity
Salum, Kaio Cezar Rodrigues
Obesidade severa
MC4R
Obesidade monogênica não sindrômica
Início da idade adulta
Mutação
Severe obesity
MC4R
Non-syndromic monogenic obesity
Adulthood-onset
Mutation
title_short Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity
title_full Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity
title_fullStr Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity
title_full_unstemmed Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity
title_sort Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity
author Salum, Kaio Cezar Rodrigues
author_facet Salum, Kaio Cezar Rodrigues
Souza, Guilherme Orofino de
Abreu, Gabriella de Medeiros
Campos Junior, Mário
Kohlrausch, Fabiana Barzotto
Carneiro, João Regis Ivar
Nogueira Neto, José Firmino
Magno, Fernanda Cristina C. Mattos
Rosado, Eliane Lopes
Palhinha, Lohanna
Monteiro, Clarissa Menezes Maya
Csbello, Giselda Maria Kalil de
Csbello, Pedro Hernán
Bozza, Patrícia Torres
Zembrzuski, Verônica Marques
Fonseca, Ana Carolina Proença da
author_role author
author2 Souza, Guilherme Orofino de
Abreu, Gabriella de Medeiros
Campos Junior, Mário
Kohlrausch, Fabiana Barzotto
Carneiro, João Regis Ivar
Nogueira Neto, José Firmino
Magno, Fernanda Cristina C. Mattos
Rosado, Eliane Lopes
Palhinha, Lohanna
Monteiro, Clarissa Menezes Maya
Csbello, Giselda Maria Kalil de
Csbello, Pedro Hernán
Bozza, Patrícia Torres
Zembrzuski, Verônica Marques
Fonseca, Ana Carolina Proença da
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Salum, Kaio Cezar Rodrigues
Souza, Guilherme Orofino de
Abreu, Gabriella de Medeiros
Campos Junior, Mário
Kohlrausch, Fabiana Barzotto
Carneiro, João Regis Ivar
Nogueira Neto, José Firmino
Magno, Fernanda Cristina C. Mattos
Rosado, Eliane Lopes
Palhinha, Lohanna
Monteiro, Clarissa Menezes Maya
Csbello, Giselda Maria Kalil de
Csbello, Pedro Hernán
Bozza, Patrícia Torres
Zembrzuski, Verônica Marques
Fonseca, Ana Carolina Proença da
dc.subject.other.pt_BR.fl_str_mv Obesidade severa
MC4R
Obesidade monogênica não sindrômica
Início da idade adulta
Mutação
topic Obesidade severa
MC4R
Obesidade monogênica não sindrômica
Início da idade adulta
Mutação
Severe obesity
MC4R
Non-syndromic monogenic obesity
Adulthood-onset
Mutation
dc.subject.en.pt_BR.fl_str_mv Severe obesity
MC4R
Non-syndromic monogenic obesity
Adulthood-onset
Mutation
description Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Geral. Laboratório de Genética Humana. Niterói, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil.
publishDate 2020
dc.date.accessioned.fl_str_mv 2020-12-18T13:47:16Z
dc.date.available.fl_str_mv 2020-12-18T13:47:16Z
dc.date.issued.fl_str_mv 2020
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv SALUM, Kaio Cezar Rodrigues et al. Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity. Frontiers in Genetics, v. 11, Article 608840, p. 1-10, Dec. 2020.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/45040
dc.identifier.issn.pt_BR.fl_str_mv 1664-8021
dc.identifier.doi.none.fl_str_mv 10.3389/fgene.2020.608840
identifier_str_mv SALUM, Kaio Cezar Rodrigues et al. Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity. Frontiers in Genetics, v. 11, Article 608840, p. 1-10, Dec. 2020.
1664-8021
10.3389/fgene.2020.608840
url https://www.arca.fiocruz.br/handle/icict/45040
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
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