To characterize further the genetic basis of progeria, thermolability studies 
were performed on three genetically distinct enzymes in crude extracts of 
cultured skin fibroblasts derived from two subjects with that syndrome. At early 
passage the progeric fibroblasts, as compared to controls, contained a 
significantly higher percentage of heat-labile glucose-6-phosphate dehydrogenase 
(12.83 plus or minus 1.72 vs 1.11 plus or minus 0.44 [mean plus or minus 
S.E.M.], p smaller than 0.001), 6-phosphogluconate dehydrogenase (9.71 plus or 
minus 0.68 vs. 0.67 plus or minus 0.22, p smaller than 0.001), and 
hypoxanthine-guanine phosphoribosyltransferase (31.41 plus or minus 1.89 vs 7.67 
plus or minus 1.71, p smaller than 0.001), and the differences were maintained 
throughout the in vitro life-span. These data, in conjunction with previous 
reports of defective HL-A antigens, indicate a widespread defect in genetic 
expression. The most likely cause appears to be an aberration in protein 
synthesis or degradation, or both, although multiple somatic mutations cannot be 
ruled out. Increased thermolability of enzymes in cultured cells may provide a 
screening test for persons predisposed to progeria and other disorders of 
premature aging.