The role of RNaseH2 in the pathogenesis of Aicardi-Goutiéres syndrome

The Aicardi-Goutières syndrome (AGS) is a rare genetic disease causing several neurological symptoms, chilblain-like skin lesions and raised INF-alpha levels. The affected children show some of the pathological symptoms at birth, although the disease is usually diagnosed after a period of normal development. AGS diagnosis is further complicated by the fact that AGS symptoms partially overlap with symptoms related to viral in utero infections. Mutations causing AGS have been mostly identified in genes coding for enzymes with nuclease activities likely relevant for the maintenance of genome stability. We aim to understand the cellular functions which are impaired by AGS mutations and how these molecular defects are related to the pathogenesis of the disease. We believe that a better understanding of the molecular basis of AGS is a necessary step to develop new therapeutical strategies and better and more specific diagnostic tools for the disease. Finally, it is expected that this research project will provide useful informations to better understand also other and more frequent autoimmune diseases with which AGS is linked.