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Case Reports
. 2025 May 21;52(1):476.
doi: 10.1007/s11033-025-10582-4.

Phenotypic and molecular characterization of a recurrent SPTAN1 mutation causing SPG91

Shih-Chun Lan  1 , Ming-Der Perng  2   3 , Yung-Yee Chang  4   5 , Ying-Fa Chen  4   5 , Min-Yu Lan  6   7   8
Affiliations
Case Reports

Phenotypic and molecular characterization of a recurrent SPTAN1 mutation causing SPG91

Shih-Chun Lan et al. Mol Biol Rep. .

Abstract

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.

Keywords: Hereditary spastic paraplegia; Membrane periodic skeleton; Protein‒protein interaction; SPG91; Spectrin heterotetramer; αII-spectrin.

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Conflict of interest statement

Declarations. Ethical approval: The study was approved by the Chang Gung Memorial Hospital Institutional Review Board (No. 100–4460 C). Written informed consent was obtained from the participants. Competing interests: The authors declare no competing interests.

References

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