title: A novel nonsense mutation in the melanocortin-4 receptor associated with obesity in a Spanish population.
abstract: BACKGROUND
  In recent years, several groups have reported dominant inheritance of obesity conferred by missense, nonsense and frameshift mutations in the melanocortin 4 receptor gene (MC4R). Hence, MC4R is involved in the most common monogenic form of human obesity described so far.
  
  
  OBJECTIVE
  In this context, we screened a Spanish population, composed of obese subjects and normal weight controls, for mutations in the MC4-R by single-strand conformational polymorphism (SSCP).
  
  
  METHODS
  Overall 313 individuals, 159 obese subjects (body mass index: BMI: 37.6 kg/m(2), 95% CI: 36.7-38.5 kg/m(2)) and 154 normal weight control subjects (BMI: 22.3 kg/m(2), 95% CI: 22.0-22.6 kg/m(2)) were screened for MC4-R mutations.
  
  
  RESULTS
  We detected a novel nonsense mutation at codon 16 of the MC4-R in an obese female (BMI: 30.0 kg/m(2)) and a previously described missense mutation (Val-253-Ile) located within the sixth trans-membrane domain of the MC4-R in a normal weight individual (BMI: 19.0 kg/m(2)). The polymorphism Val-103-Ile was detected in one obese individual, while four subjects (two cases and two controls) with the polymorphism Ile-251-Leu were found.
  
  
  CONCLUSIONS
  We have identified a novel nonsense mutation (Trp-16-Stop) that, based on previously described frameshift and nonsense mutations, most likely results in dominantly inherited obesity. Within this Spanish population, the frequency of the Ile-251-Leu polymorphism of the MC4R was similar in obese and control subjects (about 1.3%), while the polymorphism Val-103-Ile was only detected in an obese individual (0.6%).
authors.affiliation: Department of Physiology and Nutrition, University of Navarra, Pamplona, Spain. amarti@unav.es
authors.forename: A
authors.initials: A
authors.lastname: Marti
authors.forename: M S
authors.initials: MS
authors.lastname: Corbalán
authors.forename: L
authors.initials: L
authors.lastname: Forga
authors.forename: J A
authors.initials: JA
authors.lastname: Martinez
authors.forename: A
authors.initials: A
authors.lastname: Hinney
authors.forename: J
authors.initials: J
authors.lastname: Hebebrand
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D016022:Case-Control Studies; D018389:Codon, Nonsense; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009765:Obesity / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000737:chemistry / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin