Novel peroxisome proliferator-activated receptor gamma mutation in a family with familial partial lipodystrophy type 3

Objective Familial partial lipodystrophy type 3 (FPLD3) is an autosomal dominant disorder with loss of subcutaneous adipose tissue at the extremities and metabolic complications such as insulin resistance, hypertriglyceridaemia and hypertension. The aim of this study was to characterize the molecular basis of a family of 5 affected members with FPLD3. Methods A 61-year-old female index patient and her relatives were assessed by detailed clinical and biochemical examinations. Sequence analysis of the LMNA and PPARG gene was performed. Structure analysis of the identified mutation was carried out using published X-ray crystal structures. Results A novel heterozygous PPARG mutation c.1040A>C was identified in all 5 patients of the family but not in unaffected controls. The resulting amino acid substitution p.Lys347Thr is located at the ligand-binding domain (LBD) of the protein and is predicted to disrupt critical molecular interactions to the helix 12 of the LBD. Conclusions A novel PPARG mutation leading to FPLD3 is described. The results emphasize the importance of the clinical diagnosis and of further molecular genetic analyses in patients with clinical signs of FPLD but unremarkable LMNA findings.