The prevalence of melanocortin-4 receptor gene mutations in Slovak obese children and adolescents

Emil Polák, Eva Vitáriušová, Peter Celec, Zuzana Pribilincová 3 , Ľudmila Košťálová 3 , Anna Hlavatá 3 , László Kovács 3  and Ľudevít Kádaši
  • 1 Faculty of Natural Sciences, Department of Molecular Biology, Comenius University, Bratislava, Slovakia
  • 2 Institute of Molecular Physiology and Genetics, Slovak Academy of Science, Bratislava, Slovakia
  • 3 Faculty of Medicine, 2nd Department of Paediatrics, Comenius University, University Children’s Hospital, Bratislava, Slovakia
  • 4 Institute of Molecular Biomedicine, Comenius University, Bratislava, Slovakia
  • 5 Center for Molecular Medicine, Slovak Academy of Science, Bratislava, Slovakia
Emil Polák, Eva Vitáriušová, Peter Celec, Zuzana Pribilincová, Ľudmila Košťálová, Anna Hlavatá, László Kovács and Ľudevít Kádaši


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.

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The Journal of Pediatric Endocrinology and Metabolism (JPEM) is the only international journal dedicated exclusively to endocrinology in the neonatal, pediatric and adolescent age groups, and publishes the results of clinical investigations in pediatric endocrinology and basic research. JPEM publishes Review Articles, Original Research, Case Reports, Short Communications and Letters to the Editor.