Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity
BackgroundThe 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-domina...
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Frontiers Media S.A.
2020-12-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2020.608840/full |
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language |
English |
format |
Article |
sources |
DOAJ |
author |
Kaio Cezar Rodrigues Salum Kaio Cezar Rodrigues Salum Guilherme Orofino de Souza Gabriella de Medeiros Abreu Mário Campos Junior Fabiana Barzotto Kohlrausch João Regis Ivar Carneiro José Firmino Nogueira Neto Fernanda Cristina C. Mattos Magno Eliane Lopes Rosado Lohanna Palhinha Clarissa Menezes Maya-Monteiro Giselda Maria Kalil de Cabello Pedro Hernán Cabello Pedro Hernán Cabello Patrícia Torres Bozza Verônica Marques Zembrzuski Ana Carolina Proença da Fonseca Ana Carolina Proença da Fonseca |
spellingShingle |
Kaio Cezar Rodrigues Salum Kaio Cezar Rodrigues Salum Guilherme Orofino de Souza Gabriella de Medeiros Abreu Mário Campos Junior Fabiana Barzotto Kohlrausch João Regis Ivar Carneiro José Firmino Nogueira Neto Fernanda Cristina C. Mattos Magno Eliane Lopes Rosado Lohanna Palhinha Clarissa Menezes Maya-Monteiro Giselda Maria Kalil de Cabello Pedro Hernán Cabello Pedro Hernán Cabello Patrícia Torres Bozza Verônica Marques Zembrzuski Ana Carolina Proença da Fonseca Ana Carolina Proença da Fonseca Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity Frontiers in Genetics severe obesity MC4R non-syndromic monogenic obesity adulthood-onset obesity mutation |
author_facet |
Kaio Cezar Rodrigues Salum Kaio Cezar Rodrigues Salum Guilherme Orofino de Souza Gabriella de Medeiros Abreu Mário Campos Junior Fabiana Barzotto Kohlrausch João Regis Ivar Carneiro José Firmino Nogueira Neto Fernanda Cristina C. Mattos Magno Eliane Lopes Rosado Lohanna Palhinha Clarissa Menezes Maya-Monteiro Giselda Maria Kalil de Cabello Pedro Hernán Cabello Pedro Hernán Cabello Patrícia Torres Bozza Verônica Marques Zembrzuski Ana Carolina Proença da Fonseca Ana Carolina Proença da Fonseca |
author_sort |
Kaio Cezar Rodrigues Salum |
title |
Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe Obesity |
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 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Genetics |
issn |
1664-8021 |
publishDate |
2020-12-01 |
description |
BackgroundThe 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.MethodsThis 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.ResultsSignificant 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-of-function mutation, in which the minor allele poses dominant-negative effect, probably resulting in reduced cAMP activity.ConclusionThis 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. |
topic |
severe obesity MC4R non-syndromic monogenic obesity adulthood-onset obesity mutation |
url |
https://www.frontiersin.org/articles/10.3389/fgene.2020.608840/full |
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doaj-2761b05651344a41966f54f212cb79cd2020-12-09T06:21:06ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-12-011110.3389/fgene.2020.608840608840Identification of a Rare and Potential Pathogenic MC4R Variant in a Brazilian Patient With Adulthood-Onset Severe ObesityKaio Cezar Rodrigues Salum0Kaio Cezar Rodrigues Salum1Guilherme Orofino de Souza2Gabriella de Medeiros Abreu3Mário Campos Junior4Fabiana Barzotto Kohlrausch5João Regis Ivar Carneiro6José Firmino Nogueira Neto7Fernanda Cristina C. Mattos Magno8Eliane Lopes Rosado9Lohanna Palhinha10Clarissa Menezes Maya-Monteiro11Giselda Maria Kalil de Cabello12Pedro Hernán Cabello13Pedro Hernán Cabello14Patrícia Torres Bozza15Verônica Marques Zembrzuski16Ana Carolina Proença da Fonseca17Ana Carolina Proença da Fonseca18Human Genetic Laboratory, Department of General Biology, Institute of Biology, Federal Fluminense University, Niterói, BrazilHuman Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilHuman Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilHuman Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilHuman Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilHuman Genetic Laboratory, Department of General Biology, Institute of Biology, Federal Fluminense University, Niterói, BrazilClementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilDepartment of Pathology and Laboratory, Rio de Janeiro State University, Rio de Janeiro, BrazilInstitute of Nutrition Josué de Castro, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilInstitute of Nutrition Josué de Castro, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilLaboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLaboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilHuman Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilHuman Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilHuman Genetics Laboratory, Grande Rio University, Rio de Janeiro, BrazilLaboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilHuman Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilHuman Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilLaboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, BrazilBackgroundThe 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.MethodsThis 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.ResultsSignificant 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-of-function mutation, in which the minor allele poses dominant-negative effect, probably resulting in reduced cAMP activity.ConclusionThis 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.https://www.frontiersin.org/articles/10.3389/fgene.2020.608840/fullsevere obesityMC4Rnon-syndromic monogenic obesityadulthood-onset obesitymutation |