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Fragile X-associated tremor ataxia syndrome (FXTAS) is an inherited neurodegenerative disorder caused by premutation (PM) expansions (55–200 CGG repeats) of the Fragile X Mental Retardation 1 (FMR1) gene.1 Gait ataxia is a prominent and disabling feature of the syndrome, leading to increased risk of falls and eventual need for a walking aid or wheelchair. Understanding the nature of, and mechanisms underlying, gait disturbance in FXTAS has important implications for determining the risk of onset, monitoring disease progression and for the development of tailored therapies.
Accumulating evidence suggests that motor signs of FXTAS are associated with disruption to cerebellar and subcortical neural networks.2 Yet, very little research has investigated the neural mechanisms underlying functional gait disturbance in PM carriers. The current study aimed to investigate whether spatiotemporal gait characteristics were associated with cortical, cerebellar and subcortical brain volumes in a cohort of PM males with and without FXTAS.
Participants were 20 PM males (six with FXTAS) aged 26–75 years and 23 matched controls aged 26–73 years. For a detailed description of recruitment and methods including assessment of general intelligence and neurological signs, see online supplementary methods. In brief, spatiotemporal gait characteristics were assessed using a computer-based walkway measuring 593 cm long×89 cm wide with embedded pressure sensors (GAITRite; CIR Systems, New Jersey, USA). Brain MRI scans were conducted using a Phillips 3T Achieva Quasar Dual Scanner (Phillips Medical Systems, the Netherlands) located at NeuRA, Sydney. Molecular analyses have been previously described.2
Gait variables were selected based on a multidimensional framework of gait domains previously identified in a large sample of healthy older adults.3 Gait domains and their components (defined in online supplementary …