PPARG F388L, a Transactivation-Deficient Mutant, in

(FPLD) due to mutant LMNA encoding nuclear lamin A/C is characterized by adipose tissue repartitioning together with multiple metabolic disturbances, includ-ing insulin resistance and dyslipidemia. There is emerg-ing evidence that some rare mutations in peroxisome proliferator–activated receptor- (PPAR-), encoded by PPARG, might be associated with human lipodystrophy. We report a three-generation Canadian kindred ascer-tained based upon partial lipodystrophy, with a normal LMNA gene sequence. Candidate gene sequencing showed that all four affected subjects were heterozy-gous for a novel T3A mutation at PPARG nucleotide 1164 in exon 5 that predicted substitution of phenylal-anine at codon 388 by leucine (F388L). The mutation was absent from normal family members and norma