Investigating ZFYVE26 mutations in a Taiwanese cohort with hereditary spastic paraplegia

Background/purpose: Hereditary spastic paraplegia (HSP) is a heterogeneous group of inherited neurodegenerative disorders characterized by slowly progressive lower limbs spasticity and weakness. HSP type 15 (SPG15) is an autosomal recessive subtype caused by ZFYVE26 mutations. The aim of this study was to investigate the frequency and clinical and genetic features of ZFYVE26 mutations in a Taiwanese HSP cohort. Methods: Mutational analysis of the coding regions of ZFYVE26 was performed by targeted re sequencing in the 195 unrelated Taiwanese patients with HSP. All of the patients were of Han Chinese ethnicity. Clinical, neuropsychological, electrophysiological evaluations and imaging studies were collected. Results: Among the 195 patients, only one SPG15 patient was identified. The patient had a novel recessive ZFYVE26 frameshift truncating mutation, p.R1806Gfs*36 (c.5415delC), and presented with insidious onset spastic weakness of lower-extremities and cognitive impairment. Neuropsychological assessment revealed deficits in executive function, visual naming, category verbal fluency, and manual dexterity. Brain MRI showed thin corpus callosum and the ears of lynx sign. Conclusion: SPG15 accounts for approximately 0.5% (1/195) of the Taiwanese HSP cohort. This study identified the first Taiwanese SPG15 case and delineated the clinical, genetic, neuropsychological, and neuroimaging features. These findings expand the mutational spec-trum of ZFYVE26 and also broaden the knowledge of clinical and neuropsychological character-istics of SPG15. Copyright (C) 2021, Formosan Medical Association. Published by Elsevier Taiwan LLC.

Automated summary

This study identified a SPG15 patient with a novel recessive ZFYVE26 mutation in a Taiwanese HSP cohort. Neuropsychological assessment revealed cognitive deficits in the patient, while brain MRI showed specific abnormalities. The prevalence of SPG15 in Taiwanese HSP patients is approximately 0.5%.