Project

Marinesco-Sjogren's syndrome (MSS) is a rare, currently incurable, autosomal recessive disorder of childhood characterized by myopathy and cerebellar ataxia. Most of MSS patients carry SIL1 mutations causing an accumulation of unfolded proteins in the endoplasmic reticulum, the activation of unfolded protein response (UPR) and cell degeneration. The full pathogenic mechanism leading to cell death is unknown, as is which gene/protein should be targeted to treat the disease. Our aims are to identify the molecular pathways triggered by the loss of SIL1 and study their role in cell death/survival. These objectives will be obtained by applying a state-of-the-art multi-omics approach on dried blood spots (DBS) from a MSS patient and his two brothers. Data mining will be done on clustered multi-omics data using pathway analysis methods. Altered pathways will be confirmed on multiple cells and tissues using multiple approaches.