Interferon Action and Chromosome 21 Trisomy (Down Syndrome): 15 Years Later

A hypothesis relating interferon action and the chromosome 21 trisomy genotype and phenotype was presented in this journal in 1980. Since that time a number of additional genes involved in interferon action have been mapped to the distal Down Syndrome region of chromosome 21 and a growing literature has documented highly relevant pleiotropic effects of interferon in the brain. Thus, interferon continues to provide a potential basis for the phenotypic anomalies seen in the interferon supersensitive Down Syndrome patient. r, the hypothesis that ribosomal RNA gene “satellite association” induced by interferon action is involved in the induction of chromosome 21 misdistribution at meiosis, is supported by extension of the cyclic correlation of Down Syndrome prevalence and virus epidemics, first observed by Stoller & Collmann in Australia from 1942 to 1964, to incidence data gathered by the CDC in the U.S. from 1968 to 1992. In addition, data from spontaneous abortuses and gametes assembled from the literature argue for a uniquely high frequency of chromosome 21 hyperploidy which suggests that the genes present on chromosome 21 play a role in its frequent misdistribution at meiosis. Taken together, these observations provide continued support for the hypothesis presented in 1980 that interferon action could be involved in the induction of both the trisomy 21 genotype and its resultant phenotype.