Overexpression of copper-zinc superoxide dismutase in trisomy 21.

Down's syndrome (DS), the most frequent of congenital birth defects, results from the trisomy of chromosome 21 in all cells of affected patients. This disease is characterized by developmental anomalies, mental retardation and features of rapid aging, particularly in the brain, where the occurrence of Alzheimer's disease is observed in trisomy 21 patients over the age of 35. Copper-zinc superoxide dismutase (CuZnSOD) is one of the proteins encoded by chromosome 21 (21q22.1). As a consequence of gene dosage excess, CuZnSOD activity is increased by 50% in all DS tissues. This work reports the SOD activity of a population of DS patients with complete trisomy 21, partial trisomy 21, translocations and mosaicism, in order to confirm the gene dosage effect of SOD on the clinical features of DS, and to help to establish which is the critical region of chromosome 21 in DS. CuZnSOD was measured in red blood cells using the Minami and Yoshikawa method. In the population with complete trisomy 21, SOD activity was increased by 42%; in the population with partial trisomy 21, translocations and mosaicism, SOD activity was normal. In the population diagnosed as DS, but not karyotyped, SOD activity was increased by 28%. No differences between sexes or among ages were found. We conclude that the 21q22.1 segment is not the critical region responsible for DS, as we have found normal SOD activity in patients with the clinical features of DS.