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Peroxisome proliferator-activated receptor-gamma C190S mutation causes partial lipodystrophy
Angelika Lüdtke1, Janine Buettner, Wei Wu
1Department of Medicine, College of Physicians and Surgeons, Columbia University, P&S Building 10-508, New York, NY 10032, USA.
The Journal of Clinical Endocrinology and Metabolism
|March 16, 2007
Summary
A novel PPARG mutation, C190S, causes partial lipodystrophy by impairing peroxisome proliferator-activated receptor gamma (PPARγ) DNA binding and function. This leads to metabolic syndrome symptoms and altered fat distribution.
Area of Science:
- Genetics
- Molecular Biology
- Endocrinology
Background:
- Mutations in PPARG are linked to insulin resistance and familial partial lipodystrophy.
- The PPARγ protein regulates lipid and glucose metabolism and adipocyte differentiation.
Purpose of the Study:
- Identify a novel PPARG mutation in a family with partial lipodystrophy.
- Analyze the functional impact of the identified PPARG mutation.
Main Methods:
- PPARG gene sequencing in affected and unaffected individuals.
- Assessment of body composition, metabolic parameters, and hepatic steatosis.
- Evaluation of mutant PPARγ transcriptional activity and DNA binding capacity.
Main Results:
- A novel PPARG mutation, C190S, was identified in three affected family members.
- C190S PPARγ exhibited reduced transcriptional activity and impaired DNA binding.
- The mutation is located in the DNA binding domain and does not show a dominant-negative effect.
Conclusions:
- A mutation in a zinc-binding amino acid of PPARγ disrupts protein-DNA binding.
- This partial loss of function is associated with partial lipodystrophy and metabolic alterations.
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