|Title||Characterization of Rare Variants in MC4R in African American and Latino Children With Severe Early-Onset Obesity.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||De Rosa, MCaterina, Chesi, A, McCormack, S, Zhou, J, Weaver, B, McDonald, M, Christensen, S, Liimatta, K, Rosenbaum, M, Hakonarson, H, Doege, CA, Grant, SFA, Hirschhorn, JN, Thaker, VV|
|Journal||J Clin Endocrinol Metab|
|Date Published||2019 Jul 01|
CONTEXT: Mutations in melanocortin receptor (MC4R) are the most common cause of monogenic obesity in children of European ancestry, but little is known about their prevalence in children from the minority populations in the United States.
OBJECTIVE: This study aims to identify the prevalence of MC4R mutations in children with severe early-onset obesity of African American or Latino ancestry.
DESIGN AND SETTING: Participants were recruited from the weight management clinics at two hospitals and from the institutional biobank at a third hospital. Sequencing of the MC4R gene was performed by whole exome or Sanger sequencing. Functional testing was performed to establish the surface expression of the receptor and cAMP response to its cognate ligand α-melanocyte-stimulating hormone.
PARTICIPANTS: Three hundred twelve children (1 to 18 years old, 50% girls) with body mass index (BMI) >120% of 95th percentile of Centers for Disease Control and Prevention 2000 growth charts at an age
RESULTS: Eight rare MC4R mutations (2.6%) were identified in this study [R7S, F202L (n = 2), M215I, G252D, V253I, I269N, and F284I], three of which were not previously reported (G252D, F284I, and R7S). The pathogenicity of selected variants was confirmed by prior literature reports or functional testing. There was no significant difference in the BMI or height trajectories of children with or without MC4R mutations in this cohort.
CONCLUSIONS: Although the prevalence of MC4R mutations in this cohort was similar to that reported for obese children of European ancestry, some of the variants were novel.
|Alternate Journal||J. Clin. Endocrinol. Metab.|
|PubMed Central ID||PMC6546308|
|Grant List||UM1 HG006504 / HG / NHGRI NIH HHS / United States |
U54 HG006542 / HG / NHGRI NIH HHS / United States
K12 DK094723 / DK / NIDDK NIH HHS / United States
R01 DK075787 / DK / NIDDK NIH HHS / United States
K23 DK110539 / DK / NIDDK NIH HHS / United States
P30 DK026687 / DK / NIDDK NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
R01 DK052431 / DK / NIDDK NIH HHS / United States