title: Phenotypes in three pedigrees with autosomal dominant obesity caused by haploinsufficiency mutations in the melanocortin-4 receptor gene.
abstract: Recently, haploinsufficiency mutations in the melanocortin-4 receptor gene (MC4-R) were detected which were assumed to lead to the phenotype of extreme obesity. Previously, we detected three obese carriers among 306 index patients. Here we describe the detection of one haploinsufficiency carrier in an additional study group of 186 obese individuals. We subsequently genotyped and phenotyped 43 family members of these four index patients, two of whom were second-degree cousins. A total of 19 carriers were identified. Extreme obesity was the predominating phenotype. However, moderate obesity occurred in three of the carriers. No other specific phenotypic abnormalities were detected. Female haploinsufficiency carriers were heavier than male carriers in the respective families, a finding similar to findings in MC4-R-knockout mice. In conclusion, our data fully support the etiologic role of MC4-R haploinsufficiency mutations in obesity.
authors.affiliation: Clinical Research Group, Department of Child and Adolescent Psychiatry of the Philipps University Marburg, 35033 Marburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Sina
authors.forename: A
authors.initials: A
authors.lastname: Hinney
authors.forename: A
authors.initials: A
authors.lastname: Ziegler
authors.forename: T
authors.initials: T
authors.lastname: Neupert
authors.forename: H
authors.initials: H
authors.lastname: Mayer
authors.forename: W
authors.initials: W
authors.lastname: Siegfried
authors.forename: W F
authors.initials: WF
authors.lastname: Blum
authors.forename: H
authors.initials: H
authors.lastname: Remschmidt
authors.forename: J
authors.initials: J
authors.lastname: Hebebrand
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001824:Body Constitution; D015992:Body Mass Index; D002648:Child; D018388:Codon, Terminator / Q000235:genetics; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D005858:Germany; D006579:Heterozygote; D006801:Humans; D020738:Leptin / Q000097:blood; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009765:Obesity / Q000097:blood / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance; D018807:Polymorphism, Single-Stranded Conformational; D044105:Receptor, Melanocortin, Type 4; D018000:Receptors, Peptide / Q000235:genetics*; D012737:Sex Factors
chemical_list: D018388:Codon, Terminator; D020738:Leptin; D044105:Receptor, Melanocortin, Type 4; D018000:Receptors, Peptide