Scholarlink

<p>Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare inherited condition described worldwide and characterized by a wide spectrum of heterogeneity in terms of genotype and phenotype. How sacsin loss leads to neurodegeneration is still unclear, and current knowledge indicates that sacsin is involved in multiple functional mechanisms. We hence hypothesized the existence of epigenetic factors, in particular alterations in methylation patterns, that could contribute to ARSACS pathogenesis and explain the pleiotropic effects of <i>SACS</i> further than pathogenic mutations. To investigate this issue, we recruited eight patients affected by ARSACS, four characterized by early onset of the disease and four with late onset. We performed Whole Genome Bisulfite Sequencing using DNA from peripheral blood to define the methylome of patients and compared them with a control group. Our analysis showed that patients with ARSACS exhibit an altered methylation pattern and that the observed differences exist also among affected individuals with different age of onset. Our study provides valuable insights for employing epigenetic biomarkers to assess the severity and progression of this disorder and propels further investigations into the role of epigenetic processes in ARSACS pathogenesis.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Whole Blood DNA Methylation Analysis Reveals Epigenetic Changes Associated with ARSACS

  • 期刊论文

  • 发表日期：

    2025年1月24日

查看全文
  • Giulia De Riso,
  • Valentina Naef,
  • Devid Damiani,
  • Stefano Doccini,
  • Filippo M. Santorelli,
  • Daniele Galatolo

摘要

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare inherited condition described worldwide and characterized by a wide spectrum of heterogeneity in terms of genotype and phenotype. How sacsin loss leads to neurodegeneration is still unclear, and current knowledge indicates that sacsin is involved in multiple functional mechanisms. We hence hypothesized the existence of epigenetic factors, in particular alterations in methylation patterns, that could contribute to ARSACS pathogenesis and explain the pleiotropic effects of SACS further than pathogenic mutations. To investigate this issue, we recruited eight patients affected by ARSACS, four characterized by early onset of the disease and four with late onset. We performed Whole Genome Bisulfite Sequencing using DNA from peripheral blood to define the methylome of patients and compared them with a control group. Our analysis showed that patients with ARSACS exhibit an altered methylation pattern and that the observed differences exist also among affected individuals with different age of onset. Our study provides valuable insights for employing epigenetic biomarkers to assess the severity and progression of this disorder and propels further investigations into the role of epigenetic processes in ARSACS pathogenesis.