In humans, mutations in leptin, leptin receptor, prohormone convertase 1 (PC1), pro-opiomelanocortin (POMC), melanocortin 4-receptor (MC4-R), and peroxisome proliferator-activated receptor (PPAR) gamma2 genes have been described in patients with severe obesity.
We hypothesize that haploinsufficiency of SIM1, possibly acting upstream or downstream of the melanocortin 4 receptor in the PVN, is responsible for severe obesity in our subject.
In humans, mutations in leptin, leptin receptor, proopiomelanocortin (POMC), melanocortin-4 receptor (MC4R) and prohormone convertase 1 (PC1) have been described in patients with severe obesity.
Systematic screening of 431 obese children and adults for mutations in the coding sequence and the minimal core promoter of MC4R reveals that genetic variation in the transcriptionally essential region of the MC4R promoter is not a significant cause of severe obesity in humans.
To determine whether MC4R has a role in causing severe obesity in Pima Indians, we sequenced the coding region of this gene in 426 full-heritage, non-first-degree related, adult Pima Indians (300 severely obese and 126 nondiabetic nonobese control subjects).
Mutation screen of the MC4R in consecutively ascertained Austrian children and adolescents with severe obesity, to analyse the phenotype of mutation carriers and to functionally characterise novel mutations.
The purpose of the study was to investigate the association between the MC4RV103I polymorphism and the dietary intake of persons with severe obesity, which was derived by using the Willett food-frequency questionnaire.
Heterozygous MC4R mutations were associated with early-onset severe obesity, and homozygosity of the MC4R mutation Tyr157Ser resulted in morbid obesity.
The objectives of this study were to determine if mutations impairing the function of MC4R or MC3R were associated with severe obesity in North American adults.
Fifty-one unrelated probands with early onset severe obesity (body mass index (BMI) > 99th percentile; 21 girls, mean age 10.6 +/- 3.6 years) were analyzed for nucleotide variations in the MC4R coding region, by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method followed by direct DNA sequencing.
We have assessed the incidence of LEP and MC4R mutations and associated hormonal profiles, in a cohort of randomly selected Pakistani children with early onset of severe obesity.