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Selective subcortical contributions to gait impairments in males with the FMR1 premutation
  1. Rachael C Birch1,
  2. Darren R Hocking2,
  3. Kim M Cornish3,
  4. Jasmine C Menant4,5,
  5. Stephen R Lord4,5,
  6. Nellie Georgiou-Karistianis3,
  7. David E Godler6,
  8. Wei Wen7,
  9. Carolyn Rogers8,
  10. Julian N Trollor1,7
  1. 1 Department of Developmental Disability Neuropsychiatry, School of Psychiatry, UNSW Australia, Sydney, New South Wales, Australia
  2. 2 Developmental Neuromotor & Cognition Lab, School of Psychology and Public Health, La Trobe University, Melbourne, Victoria, Australia
  3. 3 Faculty of Medicine, Nursing and Health Sciences, Monash Institute for Cognitive Clinical Neuroscience & School of Psychological Sciences, Monash University, Melbourne, Victoria, Australia
  4. 4 Falls and Balance Research Group, Neuroscience Research Australia, Sydney, New South Wales, Australia
  5. 5 School of Public Health and Community Medicine, UNSW Medicine, Sydney, New South Wales, Australia
  6. 6 Cyto-molecular Diagnostic Research Laboratory, Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia
  7. 7 Centre for Healthy Brain Ageing, School of Psychiatry, UNSW Australia, Sydney, New South Wales, Australia
  8. 8 Genetics of Learning Disability Service, Hunter Genetics, Newcastle, New South Wales, Australia
  1. Correspondence to Professor Julian N Trollor, UNSW Australia, Department of Developmental Disability Neuropsychiatry, 34 Botany Street, Sydney, NSW 2052, Australia; j.trollor{at}unsw.edu.au

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Introduction

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.

Methods

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

supplementary data

[jnnp-2016-313937supp.pdf]

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 …

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