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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}

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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

supplementary data


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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  • Contributors JNT, DRH, SRL, KMC, NG-K and WW contributed to the conception and design of the project. RCB was involved in the organisation and execution of the project, design and execution of statistical analyses, and prepared the first draft of the manuscript. JCM, CR, WW and DEG also contributed to the organisation and execution of the project. All authors were involved in the review and critique of the manuscript.

  • Funding This work was supported by The Australian Research Council (Discovery Project Grant DP110103346 to KMC, JNT, NG-K, and WW); The New South Wales Institute of Psychiatry (Training Fellowship in Psychiatric Research awarded to RCB); Monash Research Fellowship and ARC Discovery Early Career Researcher Grant (DE160100042) to DRH; the Dementia Collaborative Research Centre—Assessment and Better Care, University of New South Wales as part of the Australian Government's Dementia Initiative; and the Genetics of Learning Disability (GOLD) Service. Salary for the molecular component, in part, was supported by the National Health and Medical Research Council (Project Grants 104299 and 1103389) to DEG.

  • Competing interests None declared.

  • Ethics approval Obtained from required Human Research Ethics Committees.

  • Provenance and peer review Not commissioned; externally peer reviewed.