title: A novel mutation Thr162Arg of the melanocortin 4 receptor gene in a Spanish children and adolescent population.
abstract: OBJECTIVE
  The melanocortin 4 receptor gene (MC4R) is involved in body weight regulation. While many studies associated MC4R mutations with childhood obesity, information on MC4R mutations in Spanish children and adolescents is lacking. Our objective was to screen a population of children and adolescents from the north of Spain (Navarra) for MC4R mutations and to study the phenotypes of carriers and their families. In addition, functional assays were performed for a novel MC4R mutation.
  
  
  METHODS
  The study was composed of 451 Spanish children and adolescents (49% boys), aged 5-18 year. According to the International Obesity Task Force (IOTF) criteria, the groups included 160 obese, 132 overweight and 159 normal-weight control subjects.
  
  
  RESULTS
  One novel (Thr162Arg) and three known nonsynonymous mutations in the MC4R gene (Ser30Phe, Thr150Ile, Ala244Glu) were detected heterozygously. The MC4R mutations were found in three male (one obese and two overweight) and two female subjects (one obese and one overweight). The novel mutation did not appear to lead to an impaired receptor function. An unequivocal relationship of MC4R mutations with obesity in pedigrees together with an impaired function of the encoded receptor could not be established for any of the mutations.
  
  
  CONCLUSIONS
  The presence of heterozygous MC4R mutations in obese and overweight subjects indicates that these mutations may be a susceptibility factor for obesity development, but lifestyle factors, such as exercise or sedentary activities, may modify their effect.
authors.affiliation: Department of Physiology and Nutrition, University Clinic, University of Navarra, Pamplona (Navarra), Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Ochoa
authors.forename: C
authors.initials: C
authors.lastname: Azcona
authors.forename: H
authors.initials: H
authors.lastname: Biebermann
authors.forename: H
authors.initials: H
authors.lastname: Brumm
authors.forename: C
authors.initials: C
authors.lastname: Razquin
authors.forename: A-K
authors.initials: AK
authors.lastname: Wermter
authors.forename: J A
authors.initials: JA
authors.lastname: Martínez
authors.forename: J
authors.initials: J
authors.lastname: Hebebrand
authors.forename: A
authors.initials: A
authors.lastname: Hinney
authors.forename: M J
authors.initials: MJ
authors.lastname: Moreno-Aliaga
authors.forename: A
authors.initials: A
authors.lastname: Marti
authors.forename: A
authors.initials: A
authors.lastname: Patiño
authors.forename: M
authors.initials: M
authors.lastname: Chueca
authors.forename: M
authors.initials: M
authors.lastname: Oyarzabal
authors.forename: R
authors.initials: R
authors.lastname: Pelach
mesh_terms: D000293:Adolescent; D000818:Animals; D019556:COS Cells; D016022:Case-Control Studies; D002462:Cell Membrane / Q000737:chemistry; D002648:Child; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D009765:Obesity / Q000235:genetics*; D050177:Overweight / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D044105:Receptor, Melanocortin, Type 4 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D013030:Spain; D014162:Transfection / Q000379:methods
chemical_list: D044105:Receptor, Melanocortin, Type 4; D000242:Cyclic AMP