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.