{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:12:43Z","timestamp":1791180763278,"version":"4.1.0"},"reference-count":27,"publisher":"BMJ","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2007,9]]},"abstract":"<jats:p>\n                  <jats:bold>Purpose:<\/jats:bold> Familial partial lipodystrophy caused by mutations in the <jats:italic>PPARG<\/jats:italic> gene is characterised by altered distribution of subcutaneous fat, muscular hypertrophy and symptoms of metabolic syndrome. <jats:italic>PPARG<\/jats:italic> encodes peroxisome proliferator-activated receptor (PPAR)\u03b3, a nuclear hormone receptor playing a crucial role in lipid and glucose metabolism and in several other cellular regulatory processes.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methods:<\/jats:bold>\n                  <jats:italic>PPARG<\/jats:italic> was screened for mutations by direct sequencing in two patients with lipodystrophy, one unaffected family member and 124 controls. Body composition was examined in affected patients, and they were investigated for abnormalities in laboratory results. Functional analysis of the mutant protein was assessed by determining transcriptional activity and possible interference with the wild-type protein.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results:<\/jats:bold> In two patients with familial partial lipodystrophy, we identified a nucleotide substitution in the <jats:italic>PPARG<\/jats:italic> gene. This mutation results in the substitution of aspartate by asparagine at residue 424 (D424N) in the ligand-binding domain of PPAR\u03b3. The unaffected family member and all 124 controls did not carry this mutation. D424N PPAR\u03b3 had a significantly lower ability than wild-type PPAR\u03b3 to activate a PPAR\u03b3-stimulated reporter gene, but did not exert a negative effect on the wild-type protein. Partial activation of D424N PPAR\u03b3 was achieved in the presence of the agonist rosiglitazone.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusion:<\/jats:bold> We report a new <jats:italic>PPARG<\/jats:italic> mutation, D424N, which is located in the ligand-binding domain of the protein and leads to familial partial lipodystrophy. D424N PPAR\u03b3 exhibited a loss of function, which was partially restored by adding the PPAR\u03b3 agonist rosiglitazone, suggesting possible treatment potential of this agent.<\/jats:p>","DOI":"10.1136\/jmg.2007.050567","type":"journal-article","created":{"date-parts":[[2007,8,31]],"date-time":"2007-08-31T18:13:32Z","timestamp":1188584012000},"page":"e88-e88","source":"Crossref","is-referenced-by-count":35,"title":["New <i>PPARG<\/i> mutation leads to lipodystrophy and loss of protein function that is partially restored by a synthetic ligand"],"prefix":"10.1136","volume":"44","author":[{"given":"Angelika","family":"L\u00fcdtke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Buettner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut 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