Department of Internal Medicine, Division of Nutrition and Metabolic Diseases and Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, Texas 75390
Familial partial lipodystrophies (FPL) are a heterogeneous group of
genetic disorders characterized by marked loss of subcutaneous (sc) fat
from the extremities. Affected individuals show an increased
preponderance of insulin resistance, diabetes mellitus and
dyslipidemia. Recently, lamin A/C gene mutations were found in patients
with FPL, Dunnigan variety. However, the genetic basis of other
phenotypes remains unknown. We studied peroxisome
proliferator-activated receptor- (PPAR
) gene as a candidate gene
in seven FPL patients who did not appear to have Dunnigan variety.
Analysis of the coding region of PPARG revealed C to T
heterozygous mutation at nucleotide 1273 in exon 6 which changes a
highly conserved residue, arginine at position 425 to cysteine (R425C)
in the patient FX200.21. The patient is a 64-year-old nonHispanic white
woman who developed diabetes mellitus and hypertriglyceridemia at age
32 years and lipodystrophy of the extremities and face at age 50 years.
She also had hirsutism. Anthropometry and whole body magnetic resonance
imaging revealed marked loss of sc fat particularly from the
extremities but sc truncal fat was slightly increased. None of the four
unaffected family members harbored the mutation. We conclude that
heterozygous, R425C, mutation in PPARG could be the
molecular basis for one of the familial partial lipodystrophy
phenotypes.