A Novel <i>SIL1</i> Variant (p.E342K) Associated with Marinesco-Sjogren Syndrome Impairs Protein Stability and Function.

ABSTRACT: Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessive neuromuscular disorder marked by ataxia, muscle weakness, cataracts, and often intellectual and skeletal abnormalities. It is commonly caused by loss-of-function variants in the SIL1 gene, which impair binding immunoglobulin protein (BiP) function, leading to protein misfolding and activation of the unfolded protein response. In a 2-year-old patient with typical MSS symptoms, we identified a previously unreported c.1024G>A (p.E342K) variant in SIL1 via whole-exome sequencing. The pathogenicity of this Sil1 variant was supported by evidence of structural changes revealed through in silico predictions, circular dichroism, and native gel electrophoresis. Patient-derived fibroblasts exhibited reduced Sil1 protein leve

SUBMITTER: Ruggieri AG 

PROVIDER: S-EPMC12691736 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature