What question did this study set out to answer?

To identify and characterize novel mutations in the POMC gene among patients with severe early-onset obesity and examine their functional effects on peptide processing.

August 13, 2008The Journal of Clinical Endocrinology & MetabolismOpen Access

Mutations in the Amino-Terminal Region of Proopiomelanocortin (POMC) in Patients with Early-Onset Obesity Impair POMC Sorting to the Regulated Secretory Pathway

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To identify and characterize novel mutations in the POMC gene among patients with severe early-onset obesity and examine their functional effects on peptide processing.
Screened the POMC gene in 500 patients presenting with severe early-onset obesity.
Evaluated the biosynthesis, processing, sorting, and secretion of wild-type and mutant POMC in transiently transfected beta-TC3 cells using metabolic labeling, Western blotting, and immunoassay analysis.
Identified two novel heterozygous missense mutations (C28F and L37F) in the amino-terminal region of POMC in unrelated probands and their overweight or obese family members.
Observed that both mutations impair the generation of bioactive cleavage products (C28F greater than L37F) without reducing intracellular levels of POMC.
Determined that impaired propeptide processing results from mistargeting mutant POMC to the constitutive pathway rather than the regulated secretory pathway.

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Implication

Genetic screening and functional analysis reveals novel amino-terminal POMC mutations in early-onset obesity, indicating impaired secretory trafficking causes peptide deficiency.

Cite This Study

Creemers et al. (2008) studied this question.

synapsesocial.com/papers/6aab9c1fdec6679171c53d39 https://doi.org/10.1210/jc.2008-0954

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Implication

Genetic screening and functional analysis reveals novel amino-terminal POMC mutations in early-onset obesity, indicating impaired secretory trafficking causes peptide deficiency.

Mutations in the Amino-Terminal Region of Proopiomelanocortin (POMC) in Patients with Early-Onset Obesity Impair POMC Sorting to the Regulated Secretory Pathway

Key Points

Discussion

Implication

Cite This Study

Mutations in the Amino-Terminal Region of Proopiomelanocortin (POMC) in Patients with Early-Onset Obesity Impair POMC Sorting to the Regulated Secretory Pathway

Key Points

Discussion

Implication

Cite This Study

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