TY - JOUR
T1 - Phenotypes in three pedigrees with autosomal dominant obesity caused by haploinsufficiency mutations in the melanocortin-4 receptor gene
AU - Sina, Mani
AU - Hinney, Anke
AU - Ziegler, Andreas
AU - Neupert, Tanja
AU - Mayer, Hermann
AU - Siegfried, Wolfgang
AU - Blum, Werner F.
AU - Remschmidt, Helmut
AU - Hebebrand, Johannes
N1 - Funding Information:
We thank all probands and their relatives for their participation. We thank Gerti Gerber for her excellent technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0033362016&partnerID=8YFLogxK
U2 - 10.1086/302660
DO - 10.1086/302660
M3 - Journal articles
C2 - 10577903
AN - SCOPUS:0033362016
SN - 0002-9297
VL - 65
SP - 1501
EP - 1507
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 6
ER -