We will present several gene-gene and gene-environment factors and mechanisms that are critical for adequate PPARγ expression and activity in AT and discuss how these interactions potentially contribute to the observed spectrum of FPLD3 phenotypes.
Patient 1 suffered for 18 years from devastating complications of undiagnosed type 3 familial partial lipodystrophy due to a deleterious heterozygous variant in PPARG.
Selected sequence variants in the PNR LBD associated with human retinopathies, or a mutation in the dimerization region of PPARγ LBD associated with familial partial lipodystrophy type 3, were found to disrupt PNR/PPARγ complex formation.
We evaluated the relationships between PPARγ inactivation and cellular RAS using FPLD3 patients' cells and human vascular smooth muscle cells expressing mutant or wild-type PPARγ.
Vascular placental abnormalities and newborn death in a pregnant diabetic woman with familial partial lipodystrophy type 3: a possible role for peroxisome proliferator-activated receptor γ.
Taken together with previous studies of human PPARG mutations, these findings suggest that PPAR-gamma deficiency due either to haploinsufficiency or to substantial activity loss due to dominant negative interference of the normal allele product's function can each contribute to the FPLD3 phenotype.