Scholarlink

Background <p>Demyelinating sensorimotor polyneuropathy is a complex neurological disorder characterized by progressive peripheral nerve damage and sensory loss. The frequency of spinocerebellar degeneration occurring with this phenotype is not well-documented in the literature.</p> Objective <p>This study aimed to identify genetic variants associated underlying this syndromic condition in a consanguineous family from Southern Punjab Province, Pakistan, using whole exome sequencing.</p> Methods <p>Whole exome sequencing was performed on the proband, followed by Sanger sequencing validation of identified variants in affected family members. Clinical evaluations included electroneurophysiological and magnetic resolution imaging-based assessment.</p> Results <p> Whole exome sequencing revealed four potential causative variants: two frameshift mutations in HADHA (c.874_875insGA and c.871_872delCG) and missense mutations in SLC6A6 (c.2062&#xa0;C &gt; T) and TTN (c.63917G &gt; A) genes. However, none fully cosegregated with the disease phenotype upon validation. Notably, the patients showed clinical signs of spinocerebellar degeneration without apparent structural alterations in the brain and cervical spine MRI.</p> Conclusion <p>This study highlights the genetic complexity of demyelinating sensorimotor polyneuropathy and emphasizes the need for comprehensive diagnostic approaches integrating clinical assessments with advanced genetic testing.</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 Exome Sequencing in a Pakistani Family Affected with Demyelinating Hereditary Sensorimotor Polyneuropathy with Spinocerebellar Degeneration

  • 期刊论文

  • 发表日期：

    2025年10月14日

查看全文
  • Aman Ullah,
  • Ranjha Khan,
  • Muhammad Naeem

摘要

Background

Demyelinating sensorimotor polyneuropathy is a complex neurological disorder characterized by progressive peripheral nerve damage and sensory loss. The frequency of spinocerebellar degeneration occurring with this phenotype is not well-documented in the literature.

Objective

This study aimed to identify genetic variants associated underlying this syndromic condition in a consanguineous family from Southern Punjab Province, Pakistan, using whole exome sequencing.

Methods

Whole exome sequencing was performed on the proband, followed by Sanger sequencing validation of identified variants in affected family members. Clinical evaluations included electroneurophysiological and magnetic resolution imaging-based assessment.

Results

Whole exome sequencing revealed four potential causative variants: two frameshift mutations in HADHA (c.874_875insGA and c.871_872delCG) and missense mutations in SLC6A6 (c.2062 C > T) and TTN (c.63917G > A) genes. However, none fully cosegregated with the disease phenotype upon validation. Notably, the patients showed clinical signs of spinocerebellar degeneration without apparent structural alterations in the brain and cervical spine MRI.

Conclusion

This study highlights the genetic complexity of demyelinating sensorimotor polyneuropathy and emphasizes the need for comprehensive diagnostic approaches integrating clinical assessments with advanced genetic testing.