Malle, LouiseBogunovic, Dusan
Summary
There is a growing body of evidence that shows two genes located on chromosome 21, IFNAR1 and IFNAR2, play an important role in the development of Down syndrome. Researchers on this project review current research related to these genes. They find the currently available data to be a rich resource for testable hypotheses and the interest in this work could very likely lead to new therapeutic avenues.
Abstract
Down syndrome (DS) is characterized by a collection of clinical features including intellectual disability, congenital malformations, and susceptibility to infections and autoimmune diseases. While the presence of an extra chromosome 21 is known to cause DS, the precise genetic annotation linked to specific clinical features is largely missing. However, there is growing evidence that two genes located on chromosome 21, IFNAR1 and IFNAR2, play an important role in disease pathogenesis. These genes encode the two subunits of the receptor for type I interferons (IFN-I), a group of potent antiviral and pro-inflammatory cytokines. Human monogenic diseases caused by uncontrolled IFN-I production and response have been well characterized, and they clinically overlap with DS but also have notable differences. Herein, we review the literature characterizing the role of IFN-I in DS and compare and contrast DS to other IFN-mediated conditions. The existing IFN-I literature serves as a rich resource for testable hypotheses to elucidate disease mechanisms in DS and is likely to open novel therapeutic avenues.
Conditions
Autoimmune Diseases, Infections, Intellectual Disability