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AuthorSalum, Kaio Cezar Rodrigues
AuthorSouza, Guilherme Orofino de
AuthorAbreu, Gabriella de Medeiros
AuthorCampos Junior, Mário
AuthorKohlrausch, Fabiana Barzotto
AuthorCarneiro, João Regis Ivar
AuthorNogueira Neto, José Firmino
AuthorMagno, Fernanda Cristina C. Mattos
AuthorRosado, Eliane Lopes
AuthorPalhinha, Lohanna
AuthorMonteiro, Clarissa Menezes Maya
AuthorCsbello, Giselda Maria Kalil de
AuthorCsbello, Pedro Hernán
AuthorBozza, Patrícia T.
AuthorZembrzuski, Verônica Marques
AuthorFonseca, Ana Carolina Proença da
Access date2020-12-18T13:47:16Z
Available date2020-12-18T13:47:16Z
Document date2020
CitationSALUM, 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.pt_BR
ISSN1664-8021pt_BR
URIhttps://www.arca.fiocruz.br/handle/icict/45040
Languageengpt_BR
PublisherFrontiers Mediapt_BR
Rightsopen accesspt_BR
Subject in PortugueseObesidade severapt_BR
Subject in PortugueseMC4Rpt_BR
Subject in PortugueseObesidade monogênica não sindrômicapt_BR
Subject in PortugueseInício da idade adultapt_BR
Subject in PortugueseMutaçãopt_BR
TitleIdentification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesitypt_BR
TypeArticlept_BR
DOI10.3389/fgene.2020.608840
AbstractBackground: 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.pt_BR
AffilliationUniversidade 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.pt_BR
AffilliationFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil.pt_BR
AffilliationFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil.pt_BR
AffilliationFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil.pt_BR
AffilliationUniversidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Geral. Laboratório de Genética Humana. Niterói, RJ, Brasil.pt_BR
AffilliationUniversidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Rio de Janeiro, RJ, Brasil.pt_BR
AffilliationUniversidade do Estado do Rio de Janeiro. Departamento e Laboratório de Patologia. Rio de Janeiro. RJ, Brasil.pt_BR
AffilliationUniversidade Federal do Rio de Janeiro. Instituto de Nutrição Josué de Castro. Rio de Janeiro. RJ, Brasil.pt_BR
AffilliationUniversidade Federal do Rio de Janeiro. Instituto de Nutrição Josué de Castro. Rio de Janeiro. RJ, Brasil.pt_BR
AffilliationFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.pt_BR
AffilliationFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.pt_BR
AffilliationFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil.pt_BR
AffilliationFundação 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.pt_BR
AffilliationFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.pt_BR
AffilliationFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genética Humana. Rio de Janeiro, RJ, Brasil.pt_BR
AffilliationFundação 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.pt_BR
SubjectSevere obesitypt_BR
SubjectMC4Rpt_BR
SubjectNon-syndromic monogenic obesitypt_BR
SubjectAdulthood-onsetpt_BR
SubjectMutationpt_BR


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