The Untoward Side Effects of Interferon Therapy Correlate Well with the Spectrum of Symptoms that Make up the Down Syndrome

There is an ongoing effort to identify individual genes on Chromosome 21 that may independently each subserve one of the many diverse symptoms that constitute the Down syndrome. In contrast, the interferon system points to a multigene, multilocus, system distributed across Chromosome 21 that can explain each of the individual symptoms of the Down syndrome as a consequence of the concerted action of multiple genes which share in common a role in interferon action. To date, at least ten such genes have been identified on Chromosome 21. This number is likely to grow as new genes are identified, and their role in interferon action is uncovered. The recently discovered human SIM2 gene is presented here as an example. Its Intron 3 sequence reveals a clustering of interferon response elements that suggests an unexpected role for this gene in interferon action. We also present here a comparative analysis of the complex of untoward side effects of interferon therapy that reveals a striking similarity to the spectrum of symptoms that make up the Down syndrome. Taken together, these gene mapping and clinical observations suggest the possibility that the diverse symptoms of the Down syndrome could have a surprisingly non-diverse underlying biochemistry.