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J Clin Endocrinol Metab. 2019 Feb 27. pii: jc.2018-02657. doi: 10.1210/jc.2018-02657. [Epub ahead of print]

Characterization of rare variants in MC4R in African American and/or Latino children with severe early onset obesity.

Author information

1
Columbia University Medical Center, New York, NY.
2
Children's Hospital of Philadelphia, Philadelphia, PA.
3
Boston University School of Medicine, Boston, MA.
4
Boston Children's Hospital, Boston, MA.

Abstract

CONTEXT:

Mutations in melanocortin receptor (MC4R) are the most frequent 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 and/or Latina ancestry.

DESIGN AND SETTING:

Individuals 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 and/or Sanger sequencing. Functional testing was performed to establish the surface expression of the receptor and cAMP response to its cognate ligand alpha-melanocyte-stimulating hormone.

PARTICIPANTS:

Three hundred and twelve children (1-18 years, 50% girls) with body mass index (BMI) > 120% of 95th percentile of CDC 2000 growth charts at an age < 6 years, with no known pathological cause of obesity were enrolled.

RESULTS:

Eight rare MC4R mutations (2.6%) were identified in this study (R7S, F202L (n=2), M215I, G252D, V253I, I269N, F284I), three of which have not been previously reported (G252D, F284I, R7S). The pathogenicity of selected variants was confirmed either by prior literature reports, or by functional testing. There was no significant difference in the BMI or height trajectories of children with or without MC4R mutations in this cohort.

CONCLUSIONS:

While the prevalence of MC4R mutations in this cohort was similar to that reported in obese children of European ancestry, some of the variants were novel.

PMID:
30811542
DOI:
10.1210/jc.2018-02657

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