Abstract
Melanocortin-4 receptor (MC4R) deficiency is the most frequent monogenic form of obesity. The contribution of MC4R mutations to the Slovak population has not been investigated as yet. We screened the coding sequence of the MC4R gene in a cohort of 210 Slovak obese children and adolescents. We identified four different mutations in four patients, giving a mutation detection rate of 0.95%. Of these, three were missense mutations previously identified and characterized by other research groups (p.R7C, p.S127L and p. R305W, respectively). One was a novel nonsense mutation p.W174* detected in a severely obese 7-year-old boy. This mutation was further analyzed in family segregation analysis and exhibited variable penetrance. Two known amino acid polymorphisms (p.V103I and p.I251L) were also identified in seven subjects of our cohort group. We also performed multifactorial statistical analysis to determine the influence of genotypes on standard biochemical blood markers. No significant influence was observed in carriers of DNA variants on tested parameters. We conclude that rare heterozygous MC4R mutations contribute to the onset of obesity only in a few cases in the Slovak population.
Acknowledgments
We would like to thank all the children and their families for their participation in this study. We are also grateful to pediatric endocrinologists Mária Kúseková MD†, Ľubica Tichá MD, Mária Ševecová MD, Adriana Dankovčíková MD, Marianna Debreová MD and Vilja Šandriková MD for their assistance in this study. This contribution is the result of projects implemented in the grants “Diagnostics of Socially Important Disorders in Slovakia, Based on Modern Biotechnologies” ITMS 26240220058 and “Creating Competitive Centre for research and development in the field of molecular medicine” ITMS 26240220071, supported by the Research and Developmental Operational Program funded by the ERDF. This work was also supported by VEGA 1/0497/08.
Conflict of interest: The authors declare no conflict of interest.
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