Scholarlink

Background <p>X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) is a hereditary neuropathy caused by mutations in the <i>GJB1</i> gene encoding Connexin 32 (Cx32). Despite its X-linked dominant inheritance, it has been suggested that the variable phenotypic expression of the disease in females may be due to skewed X chromosome inactivation (XCI) in Schwann cells. This pilot study aimed to examine the XCI patterns in archived sural nerve biopsies of female patients diagnosed with CMTX1 for the first time in the literature.</p> Methods <p>Two unrelated female CMTX1 patients, initially misdiagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP), with motor conduction blocks were included. <i>GJB1</i> mutations were identified using whole-exome sequencing (WES). XCI patterns were analyzed using the human androgen receptor (HUMARA) assay on archived fresh-frozen sural nerve biopsy samples performed prior the genetic diagnosis and compared with age-matched vasculitic neuropathy controls.</p> Results <p>The <i>GJB1</i> c.379&#xa0;A &gt; C mutation was identified in both CMTX1 patients. XCI analysis revealed a random XCI pattern in affected nerve tissues, with no significant differences between patients and controls.</p> Conclusion <p>Contrary to previous hypotheses, our findings suggest that XCI does not contribute to phenotypic variability in female CMTX1 patients. These results highlight the complexity of CMTX1 pathophysiology and highlight the need for further studies on alternative mechanisms regulating disease severity in females.</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

Random X chromosome inactivation in female Charcot-Marie-Tooth disease type X1: insights from sural nerve biopsy analysis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月4日

查看全文
  • Can Ebru Bekircan-Kurt,
  • Evrim Aksu-Menges,
  • Eray Taha Kumtepe,
  • Ceren Damla Durmaz,
  • Yunus Kasim Terzi,
  • Zeynep Ergul-Ulger,
  • Çagri Mesut Temucin,
  • Sevim Erdem-Ozdamar,
  • Ersin Tan,
  • Burcu Balci-Hayta

摘要

Background

X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) is a hereditary neuropathy caused by mutations in the GJB1 gene encoding Connexin 32 (Cx32). Despite its X-linked dominant inheritance, it has been suggested that the variable phenotypic expression of the disease in females may be due to skewed X chromosome inactivation (XCI) in Schwann cells. This pilot study aimed to examine the XCI patterns in archived sural nerve biopsies of female patients diagnosed with CMTX1 for the first time in the literature.

Methods

Two unrelated female CMTX1 patients, initially misdiagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP), with motor conduction blocks were included. GJB1 mutations were identified using whole-exome sequencing (WES). XCI patterns were analyzed using the human androgen receptor (HUMARA) assay on archived fresh-frozen sural nerve biopsy samples performed prior the genetic diagnosis and compared with age-matched vasculitic neuropathy controls.

Results

The GJB1 c.379 A > C mutation was identified in both CMTX1 patients. XCI analysis revealed a random XCI pattern in affected nerve tissues, with no significant differences between patients and controls.

Conclusion

Contrary to previous hypotheses, our findings suggest that XCI does not contribute to phenotypic variability in female CMTX1 patients. These results highlight the complexity of CMTX1 pathophysiology and highlight the need for further studies on alternative mechanisms regulating disease severity in females.