Marinesco-Sjögren Syndrome: A Novel SIL1 Variant with In Silico Analysis and Review of the Literature
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View abstract on PubMed
Summary
This summary is machine-generated.Marinesco-Sjögren syndrome (MSS) is a rare genetic disorder. A novel SIL1 splice-site variant was identified, causing protein truncation and severe disease, highlighting the need for comprehensive genetic diagnostics.
Area Of Science
- Genetics
- Molecular Biology
- Neurology
Background
- Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessive neurodegenerative disorder.
- It is characterized by cerebellar ataxia, congenital cataracts, developmental delay, hypotonia, and progressive myopathy.
- Pathogenic variants in the SIL1 gene, encoding an endoplasmic reticulum co-chaperone, are the primary cause of MSS.
Purpose Of The Study
- To present a comprehensive case study of a Turkish pediatric patient with MSS.
- To investigate the genetic, bioinformatic, and structural implications of a novel SIL1 variant.
- To enhance understanding of genotype-phenotype correlations in MSS.
Main Methods
- Whole-exome sequencing (WES) and Sanger sequencing for variant identification and confirmation.
- In silico annotation using multiple bioinformatics tools (Genomize, InterVar, Franklin, VarSome, ClinVar, OMIM, PubMed).
- Structural modeling (Phyre2, I-TASSER) to predict the impact of the variant on protein structure and function.
Main Results
- A homozygous splice-site variant (SIL1 c.453+1G>T) was identified in the patient.
- Bioinformatic analysis classified the variant as pathogenic according to ACMG guidelines.
- Structural modeling revealed that the variant leads to protein truncation, loss of critical ARM repeats, and impaired chaperone function, consistent with the patient's severe MSS phenotype.
Conclusions
- The identified SIL1 splice-site variant expands the known mutational spectrum for MSS.
- Splicing defects in SIL1 are confirmed to cause severe MSS phenotypes, including early-onset ataxia and cataracts.
- Integrated genomic, structural, and clinical data are crucial for diagnosing rare neurogenetic disorders like MSS.
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