This Article Full Text Full Text (PDF) All Versions of this Article: 92/9/3689    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hainerová, I. Articles by Pedersen, O. Search for Related Content PubMed PubMed Citation Articles by Hainerová, I. Articles by Pedersen, O. Related Collections Obesity Neuroendocrinology and Pituitary Pediatric Endocrinology

Melanocortin 4 Receptor Mutations in Obese Czech Children: Studies of Prevalence, Phenotype Development, Weight Reduction Response, and Functional Analysis

Irena Hainerová, Lesli H. Larsen, Birgitte Holst, Marie Finková, Vojtch Hainer, Jan Lebl, Torben Hansen and Oluf Pedersen

Department of Pediatrics and Center for Research of Diabetes, Metabolism, and Nutrition (I.H., M.F.), Third Faculty of Medicine, Charles University, 100 34 Prague 10, Czech Republic; Steno Diabetes Center and Hagedorn Research Institute (L.H.L., T.H., O.P.), Gentofte, DK-2820 Copenhagen, Denmark; Department of Pharmacology (B.H.), University of Copenhagen, DK-2200 Copenhagen, Denmark; Obesity Management Center (V.H.), Institute of Endocrinology, 116 94 Prague, Czech Republic; Department of Pediatrics (J.L.), Second Faculty of Medicine, Charles University, 15006 Prague 5, Czech Republic; Danish Epidemiology Science Center (L.H.L.), Institute of Preventive Medicine, Copenhagen University Hospital, DK-1357 Copenhagen, Denmark; and Faculty of Health (O.P.), University of Aarhus, DK-8000 C Aarhus, Denmark

Address all correspondence and requests for reprints to: Irena Hainerová, M.D., Department of Pediatrics, robárova 50, 100 34 Prague 10, Czech Republic. E-mail: ihainer{at}hotmail.com.

Background: Mutations in the melanocortin 4 receptor gene (MC4R) represent the most common known cause of monogenic human obesity.

Aims: The aims of this study were the following: 1) to estimate the prevalence of MC4R mutations in obese Czech children; 2) to evaluate phenotypic features of the mutation carriers; 3) to compare weight, height, and body mass index of MC4R mutation carriers with noncarriers in longitudinal studies; 4) to determine the effect of a weight management program among MC4R mutation carriers; and 5) to perform a functional analysis of a novel variant.

Subjects and Methods: We analyzed the coding region of MC4R in a cohort of 289 Czech children and adolescents with early-onset obesity by direct sequencing. Information on weight, height, body mass index, baseline biochemical data, and a weight loss follow-up study was obtained. In vitro functional analysis of one novel variant was performed.

Results: We identified six different mutations in seven probands: one novel missense mutation Cys84Arg and five previously reported variants, Arg7Cys, Ser19fsdelA, Phe51Leu, Ser127Leu, and Gly181Asp. The Gly181Asp variant was detected in one homozygous carrier from unrelated parents. None of the mutation carriers fulfilled the MC4R syndrome criteria. A comparison of anthropometrics in mutation carriers and noncarriers during 13 yr of follow-up did not reveal any significant differences. MC4R mutation carriers exhibited a similar ability to lose weight as obese noncarriers. The novel variant Cys84Arg showed a significant reduction in cAMP signal properties of the MC4R.

Conclusions: Among obese Czech children, we found a prevalence of 2.4% of MC4R homozygous and heterozygous mutations and showed a similar response to diet management of MC4R mutation carriers and noncarriers.

This article has been cited by other articles:

				V. Hainer, H. Toplak, and A. Mitrakou Treatment Modalities of Obesity: What fits whom? Diabetes Care, February 1, 2008; 31(Supplement_2): S269 - S277. [Abstract] [Full Text] [PDF]