Which are the causes of Marinesco-Sjögren Syndrome?

Marinesco-Sjögren Syndrome (MSS) is a rare genetic disorder that affects multiple systems in the body. It is characterized by a combination of symptoms including cerebellar ataxia, cataracts, intellectual disability, and muscle weakness. The exact cause of MSS is not fully understood, but it is believed to be primarily caused by mutations in the SIL1 gene.

The SIL1 gene provides instructions for producing a protein called SIL1, which is involved in the proper folding and assembly of other proteins in the endoplasmic reticulum (ER) of cells. The ER is responsible for synthesizing and processing proteins that are essential for various cellular functions. Mutations in the SIL1 gene disrupt the normal function of the SIL1 protein, leading to impaired protein folding and ER stress.

ER stress refers to an imbalance between the protein-folding capacity of the ER and the demand for properly folded proteins. When the ER is overwhelmed with misfolded or unfolded proteins, it triggers a cellular response called the unfolded protein response (UPR). The UPR aims to restore ER homeostasis by increasing the production of chaperone proteins, which assist in protein folding, and by reducing protein synthesis.

In MSS, mutations in the SIL1 gene result in a dysfunctional SIL1 protein, leading to chronic ER stress and activation of the UPR. This prolonged ER stress can have detrimental effects on various tissues and organs, contributing to the development of the characteristic features of MSS.

Although SIL1 gene mutations are the primary cause of MSS, it is important to note that not all individuals with MSS have identifiable mutations in this gene. This suggests that there may be other genetic or environmental factors that can contribute to the development of the syndrome.

Research is ongoing to further understand the underlying mechanisms of MSS and to identify additional genes or factors that may be involved. By gaining a deeper understanding of the causes of MSS, researchers hope to develop targeted therapies that can alleviate symptoms and improve the quality of life for individuals affected by this rare disorder.