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AuthorMohammed, Idris
AuthorHaris, Basma
AuthorAl-Barazenji, Tara
AuthorVasudeva, Dhanya
AuthorTomei, Sara
AuthorAl Azwani, Iman
AuthorDauleh, Hajar
AuthorShehzad, Saira
AuthorChirayath, Shiga
AuthorMohamadsalih, Ghassan
AuthorPetrovski, Goran
AuthorKhalifa, Amel
AuthorLove, Donald R
AuthorAl-Shafai, Mashael
AuthorHussain, Khalid
Available date2023-10-29T10:56:29Z
Publication Date2023-06-17
Publication NameThe Journal of Clinical Endocrinology & Metabolism
Identifierhttp://dx.doi.org/10.1210/clinem/dgad366
CitationIdris Mohammed, Basma Haris, Tara Al-Barazenji, Dhanya Vasudeva, Sara Tomei, Iman Al Azwani, Hajar Dauleh, Saira Shehzad, Shiga Chirayath, Ghassan Mohamadsalih, Goran Petrovski, Amel Khalifa, Donald R Love, Mashael Al-Shafai, Khalid Hussain, Understanding the Genetics of Early-Onset Obesity in a Cohort of Children From Qatar, The Journal of Clinical Endocrinology & Metabolism, 2023;, dgad366, https://doi.org/10.1210/clinem/dgad366
ISSN0021-972X
URIhttp://hdl.handle.net/10576/48854
AbstractMonogenic 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. To unravel the genetic causes of early onset obesity in the population of Qatar. 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. 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, seven 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 five patients. 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 which revealed novel obesity variants in this understudied population. Functional studies will be required to elucidate the molecular mechanism of their pathogenicity.
SponsorThis research was supported by the Qatar National Research Fund (QNRF-NPRP 10-6100017-AXX) and a research grant from Amryt awarded to Professor Khalid Hussain.
Languageen
PublisherOxford University Press
SubjectMC4R
Monogenic obesity
Qatar
childhood obesity
severe obesity
TitleUnderstanding the genetics of early onset obesity in a cohort of children from Qatar.
TypeArticle
ESSN1945-7197
dc.accessType Open Access


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