Deletion of codons 88-92 of the melanocortin-4 receptor gene: a novel deleterious mutation in an obese female

Patricia A Donohoue; Ya-Xiong Tao; Malia Collins; Giles S H Yeo; Stephen O'Rahilly; Deborah L Segaloff

doi:10.1210/jc.2003-030903

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Deletion of codons 88-92 of the melanocortin-4 receptor gene: a novel deleterious mutation in an obese female

Journal article

Open access

Peer reviewed

Deletion of codons 88-92 of the melanocortin-4 receptor gene: a novel deleterious mutation in an obese female

Patricia A Donohoue, Ya-Xiong Tao, Malia Collins, Giles S H Yeo, Stephen O'Rahilly and Deborah L Segaloff

The journal of clinical endocrinology and metabolism, Vol.88(12), pp.5841-5845

12/2003

DOI: 10.1210/jc.2003-030903

PMID: 14671178

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Abstract

Genetic and pharmacological studies have shown that the melanocortin-4 receptor (MC4R) is an important regulator of food intake and energy homeostasis. Consistent with these studies, several mutations of the MC4R gene have been identified as being associated with early-onset severe obesity. We report here the first in-frame deletion mutation of the MC4R gene (delta88-92) in an obese female patient with onset of obesity at less than 5 yr of age. Functional analysis revealed that the mutant receptor is expressed well on the cell surface but completely devoid of ligand binding and cAMP generation in response to agonist stimulation. We conclude that this novel mutation is the cause of obesity of this patient.

Binding, Competitive

Cell Line

Base Sequence - genetics

Humans

Middle Aged

Male

Receptor, Melanocortin, Type 4 - metabolism

Receptor, Melanocortin, Type 4 - agonists

Receptor, Melanocortin, Type 4 - genetics

Amino Acid Sequence - genetics

Obesity - genetics

Cyclic AMP - biosynthesis

Gene Deletion

Adolescent

Adult

Female

Ligands

Codon - genetics

Mutation

Details

Title: Subtitle: Deletion of codons 88-92 of the melanocortin-4 receptor gene: a novel deleterious mutation in an obese female
Creators: Patricia A Donohoue - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA. patricia-donohoue@uiowa.edu
Ya-Xiong Tao
Malia Collins
Giles S H Yeo
Stephen O'Rahilly
Deborah L Segaloff
Resource Type: Journal article
Publication Details: The journal of clinical endocrinology and metabolism, Vol.88(12), pp.5841-5845
DOI: 10.1210/jc.2003-030903
PMID: 14671178
ISSN: 0021-972X
eISSN: 1945-7197
Grant note: HD29569 / NICHD NIH HHS HD22196 / NICHD NIH HHS DK25295 / NIDDK NIH HHS
Language: English
Date published: 12/2003
Academic Unit: Molecular Physiology and Biophysics; Obstetrics and Gynecology; Ophthalmology and Visual Sciences
Record Identifier: 9984083850402771

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