Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene.

@article{Farooqi2003ClinicalSO,
  title={Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene.},
  author={I Sadaf Farooqi and Julia M Keogh and Giles S. H. Yeo and Emma J Lank and Tim Cheetham and Stephen O’Rahilly},
  journal={The New England journal of medicine},
  year={2003},
  volume={348 12},
  pages={
          1085-95
        }
}
BACKGROUND Melanocortin 4 receptor (MC4R) deficiency is the commonest monogenic form of obesity. However, the clinical spectrum and mode of inheritance have not been defined, pathophysiological mechanisms leading to obesity are poorly understood, and there is little information regarding genotype-phenotype correlations. METHODS We determined the nucleotide sequence of the MC4R gene in 500 probands with severe childhood obesity. Family studies were undertaken to examine cosegregation of… 
View on PubMed
cogsci.ucsd.edu
1,446 Citations
Highly Influential Citations
91
Background Citations
503
Methods Citations
14
Results Citations
38

1,446 Citations

Citation Type

Citation Type

Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor.
TLDR
The prevalence of pathogenic LEPR mutations in a cohort of subjects with severe, early-onset obesity was 3%.
Melanocortin‐4 Receptor Gene Mutations in a Dutch Cohort of Obese Children
TLDR
It is concluded that rare heterozygous mutations in the coding sequence of MC4R account for some severe obesity cases in the Dutch population, which are difficult to recognize in a clinical setting.
Homozygous null mutation of the melanocortin-4 receptor and severe early-onset obesity.
Melanocortin 3 receptor gene and melanocortin 4 receptor gene mutations: the Asian Perspective
  • Y. Lee
  • Biology, Medicine
    Diabetes/metabolism research and reviews
  • 2012
TLDR
Evidence is provided that MC3R can be one of the genes which contributes to increased adiposity, and exert an effect on the human phenotype, and the pathogenic role of melanocortin 3 receptor gene (MC3R) mutations in human obesity is not as well described and accepted as MC4R mutations, though it is gradually gaining ground.
The prevalence of melanocortin-4 receptor gene mutations in Slovak obese children and adolescents
TLDR
It is concluded that rare heterozygous MC4R mutations contribute to the onset of obesity only in a few cases in the Slovak population.
Prevalence of Melanocortin-4 Receptor Deficiency in Europeans and Their Age-Dependent Penetrance in Multigenerational Pedigrees
TLDR
A robust estimate of age-related penetrance for MC4R deficiency is established and a generational effect on penetrance is demonstrated, which may relate to the development of an “obesogenic” environment.
High prevalence of leptin and melanocortin-4 receptor gene mutations in children with severe obesity from Pakistani consanguineous families.
Sporadic mutations in melanocortin receptor 3 in morbid obese individuals
TLDR
It is suggested that, in humans, MC3R mutations may be a cause of a dominantly inherited form of obesity, however, this association as well as the specific phenotypic characteristics resulting from these mutations need to be further evaluated in larger series of obese subjects.
Obesity-Associated GNAS Mutations and the Melanocortin Pathway.
TLDR
Screening of children with severe obesity for GNAS deficiency may allow early diagnosis, improving clinical outcomes, and melanocortin agonists may aid in weight loss.
Melanocortin-4 receptor in energy homeostasis and obesity pathogenesis.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 40 REFERENCES
Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency.
TLDR
The nucleotide sequence of the entire coding region of the MC4R gene is determined in 243 subjects with severe, early-onset obesity, resulting in a syndrome of hyperphagic obesity in humans that can present with either dominant or recessive patterns of inheritance.
Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity.
TLDR
It is demonstrated that MC4-R mutations are a frequent but heterogeneous genetic cause of morbid obesity and transmission in the families of the carriers indicates a variable expressivity that is not related to the functional severity of the mutations.
Melanocortin 4 receptor sequence variations are seldom a cause of human obesity: the Swedish Obese Subjects, the HERITAGE Family Study, and a Memphis cohort.
TLDR
The results do not support the prevailing notion that sequence variation in the melanocortin 4 receptor gene is a frequent cause of human obesity.
Molecular scanning for mutations in the melanocortin-4 receptor gene in obese/diabetic Japanese.
TLDR
Results suggest that mutations including V103I in the MC4R gene are not a major cause of obesity or diabetes in Japanese.
Molecular scanning for mutations in the melanocortin‐4 receptor gene in obese/diabetic Japanese
TLDR
Results suggest that mutations including V103I in the MC4R gene are not a major cause of obesity or diabetes in Japanese.
Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans.
TLDR
The data indicate that mutations in the MC4-R are not uncommon, and support the evidence for dominantly inherited obesity as revealed by the three obese probands with haplo-insufficiency, the functional significance of the missense mutations remains to be determined.
Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene
TLDR
It is inferred that molecular defects in prohormone conversion may represent a generic mechanism for obesity, common to humans and rodents.
Congenital leptin deficiency is associated with severe early-onset obesity in humans
TLDR
The severe obesity found in two severely obese children who are members of the same highly consanguineous pedigree provides the first genetic evidence that leptin is an important regulator of energy balance in humans.
Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans
TLDR
These findings represent the first examples of a genetic defect within the POMC gene and define a new monogenic endocrine disorder resulting in early–onset obesity, adrenal insufficiency and red hair pigmentation.
A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction
TLDR
A homozygous mutation in the human leptin receptor gene results in a truncated leptin receptor lacking both the transmembrane and the intracellular domains, which indicates that leptin is an important physiological regulator of several endocrine functions in humans.
...
1
2
3
4
...