Case Report: Novel homozygous pathogenic variant of the SPG20 gene causes the Troyer syndrome in China.

Authors

Lina Zhu, Siqi Hu, Xinyang Jiang, Rujie Gu, Yongxia Wang, Shufang Zhang, Fujun Peng, Xiuwei Ma

Published in

Frontiers in genetics. Volume 17. Pages 1842902. Epub Jul 02, 2026.

Abstract

Hereditary spastic paraplegia (HSP) comprises a group of neurodegenerative disorders characterized by progressive spasticity of the lower limbs. Troyer syndrome (MIM #275900), an autosomal recessive form of complicated HSP, was initially described in the Old Order Amish population. The syndrome is associated with a spectrum of clinical manifestations, including spastic paraplegia, muscle atrophy, dysarthria, intellectual disability, and abnormal white matter on neuroimaging. The causative gene for Troyer syndrome has been identified as SPG20, which encodes the spartin protein. Spartin plays a pivotal role in lipid droplet degradation and mitochondrial function. Here, we report the clinical and molecular features of the second documented case of Troyer syndrome in China. The patient, a 5-year-8-month-old Han Chinese girl, presented with delayed psychomotor development, abnormal gait, and a history of febrile seizures. Whole-exome sequencing revealed a novel homozygous pathogenic variant, c.1734-1G>C, in SPG20, leading to a frameshift and the expression of a truncated protein. This variant was absent from multiple population databases of healthy individuals, and both parents were heterozygous carriers without clinical manifestations. Functional studies in cells transfected with SPG20 constructs demonstrated that the variant spartin protein failed to localize to lipid droplets, leading to their accumulation. This functional impairment may contribute to the pathogenesis of Troyer syndrome. Our findings expand the variant spectrum of SPG20 and provide further insight into the genotype-phenotype relationship in Troyer syndrome, highlighting the critical role of spartin in lipid metabolism and neuronal function.

PMID:
42460154
Bibliographic data and abstract were imported from PubMed on 16 Jul 2026.

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