Deciphering the mechanism of immune dysfunction in Vici syndrome

Vici syndrome (ViciS) is a rare multisystem disorder characterized by callosal agenesis, cataracts, combined immunodeficiency, cardiomyopathy, hypopigmentation, psychomotor retardation, seizures, severe and recurrent infections. Recently, in patients with ViciS have identified mutations in the gene EPG-5 on chromosome 18q12.3. EPG-5 is involved in the regulation of autophagy and is indispensable for the formation of autolysosomes. Mutations in EPG-5 may be responsible for many anatomical and functional defects. Here, we aim to understand the cellular and molecular mechanisms of immune deficiency in ViciS patients and to correlate EPG-5 and innate / adaptive immune responses by analyzing specific molecular pathways. In particular we are interested in understanding how the mutations of EPG-5 affect the response to TLRs, the process of endocytosis and the consequences of the mutation on the amount of the transcript and protein level.