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Understanding the Genetics of Early-Onset Obesity in a Cohort of Children From Qatar
CONTEXT: Monogenic obesity is a rare form of obesity due to pathogenic variants in genes implicated in the leptin–melanocortin signaling pathway and accounts for around 5% of severe early-onset obesity. Mutations in the genes encoding the MC4R, leptin, and leptin receptor are commonly reported in va...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10655519/ https://www.ncbi.nlm.nih.gov/pubmed/37329217 http://dx.doi.org/10.1210/clinem/dgad366 |
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author | Mohammed, Idris Haris, Basma Al-Barazenji, Tara Vasudeva, Dhanya Tomei, Sara Al Azwani, Iman Dauleh, Hajar Shehzad, Saira Chirayath, Shiga Mohamadsalih, Ghassan Petrovski, Goran Khalifa, Amel Love, Donald R Al-Shafai, Mashael Hussain, Khalid |
author_facet | Mohammed, Idris Haris, Basma Al-Barazenji, Tara Vasudeva, Dhanya Tomei, Sara Al Azwani, Iman Dauleh, Hajar Shehzad, Saira Chirayath, Shiga Mohamadsalih, Ghassan Petrovski, Goran Khalifa, Amel Love, Donald R Al-Shafai, Mashael Hussain, Khalid |
author_sort | Mohammed, Idris |
collection | PubMed |
description | CONTEXT: Monogenic obesity is a rare form of obesity due to pathogenic variants in genes implicated in the leptin–melanocortin signaling pathway and accounts for around 5% of severe early-onset obesity. Mutations in the genes encoding the MC4R, leptin, and leptin receptor are commonly reported in various populations to cause monogenic obesity. Determining the genetic cause has important clinical benefits as novel therapeutic interventions are now available for some forms of monogenic obesity. OBJECTIVE: To unravel the genetic causes of early-onset obesity in the population of Qatar. METHODS: In total, 243 patients with early-onset obesity (above the 95% percentile) and age of onset below 10 years were screened for monogenic obesity variants using a targeted gene panel, consisting of 52 obesity-related genes. RESULTS: Thirty rare variants potentially associated with obesity were identified in 36 of 243 (14.8%) probands in 15 candidate genes (LEP, LEPR, POMC, MC3R, MC4R, MRAP2, SH2B1, BDNF, NTRK2, DYRK1B, SIM1, GNAS, ADCY3, RAI1, and BBS2). Twenty-three of the variants identified were novel to this study and the rest, 7 variants, were previously reported in literature. Variants in MC4R were the most common cause of obesity in our cohort (19%) and the c.485C>T p.T162I variant was the most frequent MC4R variant seen in 5 patients. CONCLUSION: We identified likely pathogenic/pathogenic variants that seem to explain the phenotype of around 14.8% of our cases. Variants in the MC4R gene are the commonest cause of early-onset obesity in our population. Our study represents the largest monogenic obesity cohort in the Middle East and revealed novel obesity variants in this understudied population. Functional studies will be required to elucidate the molecular mechanism of their pathogenicity. |
format | Online Article Text |
id | pubmed-10655519 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-106555192023-06-17 Understanding the Genetics of Early-Onset Obesity in a Cohort of Children From Qatar Mohammed, Idris Haris, Basma Al-Barazenji, Tara Vasudeva, Dhanya Tomei, Sara Al Azwani, Iman Dauleh, Hajar Shehzad, Saira Chirayath, Shiga Mohamadsalih, Ghassan Petrovski, Goran Khalifa, Amel Love, Donald R Al-Shafai, Mashael Hussain, Khalid J Clin Endocrinol Metab Clinical Research Article CONTEXT: Monogenic obesity is a rare form of obesity due to pathogenic variants in genes implicated in the leptin–melanocortin signaling pathway and accounts for around 5% of severe early-onset obesity. Mutations in the genes encoding the MC4R, leptin, and leptin receptor are commonly reported in various populations to cause monogenic obesity. Determining the genetic cause has important clinical benefits as novel therapeutic interventions are now available for some forms of monogenic obesity. OBJECTIVE: To unravel the genetic causes of early-onset obesity in the population of Qatar. METHODS: In total, 243 patients with early-onset obesity (above the 95% percentile) and age of onset below 10 years were screened for monogenic obesity variants using a targeted gene panel, consisting of 52 obesity-related genes. RESULTS: Thirty rare variants potentially associated with obesity were identified in 36 of 243 (14.8%) probands in 15 candidate genes (LEP, LEPR, POMC, MC3R, MC4R, MRAP2, SH2B1, BDNF, NTRK2, DYRK1B, SIM1, GNAS, ADCY3, RAI1, and BBS2). Twenty-three of the variants identified were novel to this study and the rest, 7 variants, were previously reported in literature. Variants in MC4R were the most common cause of obesity in our cohort (19%) and the c.485C>T p.T162I variant was the most frequent MC4R variant seen in 5 patients. CONCLUSION: We identified likely pathogenic/pathogenic variants that seem to explain the phenotype of around 14.8% of our cases. Variants in the MC4R gene are the commonest cause of early-onset obesity in our population. Our study represents the largest monogenic obesity cohort in the Middle East and revealed novel obesity variants in this understudied population. Functional studies will be required to elucidate the molecular mechanism of their pathogenicity. Oxford University Press 2023-06-17 /pmc/articles/PMC10655519/ /pubmed/37329217 http://dx.doi.org/10.1210/clinem/dgad366 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Clinical Research Article Mohammed, Idris Haris, Basma Al-Barazenji, Tara Vasudeva, Dhanya Tomei, Sara Al Azwani, Iman Dauleh, Hajar Shehzad, Saira Chirayath, Shiga Mohamadsalih, Ghassan Petrovski, Goran Khalifa, Amel Love, Donald R Al-Shafai, Mashael Hussain, Khalid Understanding the Genetics of Early-Onset Obesity in a Cohort of Children From Qatar |
title | Understanding the Genetics of Early-Onset Obesity in a Cohort of Children From Qatar |
title_full | Understanding the Genetics of Early-Onset Obesity in a Cohort of Children From Qatar |
title_fullStr | Understanding the Genetics of Early-Onset Obesity in a Cohort of Children From Qatar |
title_full_unstemmed | Understanding the Genetics of Early-Onset Obesity in a Cohort of Children From Qatar |
title_short | Understanding the Genetics of Early-Onset Obesity in a Cohort of Children From Qatar |
title_sort | understanding the genetics of early-onset obesity in a cohort of children from qatar |
topic | Clinical Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10655519/ https://www.ncbi.nlm.nih.gov/pubmed/37329217 http://dx.doi.org/10.1210/clinem/dgad366 |
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