Intrafamilial Phenotypic Variation in Taiwanese Patients with Hereditary Spastic Paraplegia and Charcot-Marie-Tooth Disease Due to KIF5A Mutations: A Cross-Sectional Observational Study
Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Hereditary spastic paraplegia (HSP) type 10 (SPG10) is an autosomal-dominantly inherited disease caused by pathogenic variants in KIF5A , presenting as either pure or complex HSP. OBJECTIVES: This study aims to investigate the clinical and genetic features of KIF5A variants in a Taiwanese cohort diagnosed with HSP. MATERIALS AND METHODS: We analyzed KIF5A coding regions in 219 unrelated Taiwanese patients clinically diagnosed with HSP using a targeted resequencing panel. Clinical, electrophysiological, and neuroimaging features of patients with SPG10 were characterized. RESULTS: Only one (0.5%) patient carried a heterozygous KIF5A variant, c.838C>T (p.Arg280Cys). This patient had a complex HSP phenotype with sensorimotor polyneuropathy, neuropathic pain, appendicular ataxia, and late disease onset at 39 years. Three family members also carried the variant, with one presented with HSP and two with axonal polyneuropathy, diagnosed as axonal Charcot-Marie-Tooth disease (CMT2). CONCLUSIONS: SPG10 is a rare HSP subtype in the Taiwanese population. This is the first report of SPG10 in Taiwan, highlighting the coexistence of SPG10 and CMT2 within a single family and the significant intra-familial phenotypic variation.
Source: Acta Neurologica Taiwanica
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4411327228