Scholarlink

Background <p>Spectrins are ubiquitous cytoskeleton proteins found in all metazoan cells. αII-spectrin, encoded by SPTAN1, is the pivotal protein responsible for organization of the axonal cytoskeleton. Monoallelic SPTAN1 mutations cause various inherited neurological diseases, including spastic paraplegia 91 (SPG91), a type of hereditary spastic paraplegia (HSP).</p> Methods and results <p>We reported two patients with SPG91 caused by the SPTAN1 mutation c.55&#xa0;C &gt; T (p.Arg19Trp), who presented with lower limb spasticity and polyneuropathy. An analysis of the patients reported in the literature in addition to the present patients revealed that SPTAN1 p.Arg19Trp was specific for an HSP phenotype, with 35% of the combined patients with sensory‒motor polyneuropathy and 30% with cerebellar ataxia. In computational simulations, this variant was predicted to perturb the stability of αII/β spectrin heterotetramerization but did not destabilize the tetramerization domain of αII-spectrin.</p> Conclusions <p>Our findings on genotype‒phenotype correlations and genetic effects on molecular characteristics may provide important insights into the exploration of αII-spectrin-related neurological diseases.</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

Phenotypic and molecular characterization of a recurrent SPTAN1 mutation causing SPG91

  • 期刊论文

  • 发表日期：

    2025年5月21日

查看全文
  • Shih-Chun Lan,
  • Ming-Der Perng,
  • Yung-Yee Chang,
  • Ying-Fa Chen,
  • Min-Yu Lan

摘要

Background

Spectrins are ubiquitous cytoskeleton proteins found in all metazoan cells. αII-spectrin, encoded by SPTAN1, is the pivotal protein responsible for organization of the axonal cytoskeleton. Monoallelic SPTAN1 mutations cause various inherited neurological diseases, including spastic paraplegia 91 (SPG91), a type of hereditary spastic paraplegia (HSP).

Methods and results

We reported two patients with SPG91 caused by the SPTAN1 mutation c.55 C > T (p.Arg19Trp), who presented with lower limb spasticity and polyneuropathy. An analysis of the patients reported in the literature in addition to the present patients revealed that SPTAN1 p.Arg19Trp was specific for an HSP phenotype, with 35% of the combined patients with sensory‒motor polyneuropathy and 30% with cerebellar ataxia. In computational simulations, this variant was predicted to perturb the stability of αII/β spectrin heterotetramerization but did not destabilize the tetramerization domain of αII-spectrin.

Conclusions

Our findings on genotype‒phenotype correlations and genetic effects on molecular characteristics may provide important insights into the exploration of αII-spectrin-related neurological diseases.