Neurodegenerative diseases

In collaboration with The Alfred Neurosciences department, we published a paper in *Neurology, examining the neuropathology of a newly described syndrome CANVAS – cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome.

We identified by pathologic examination that the mechanism responsible for the disease is related to a loss of specific neurons.

The work was highlighted at the 2014 International Congress of Neuropathology meeting in Rio de Janeiro to alert neuropathologists to this newly described condition. Our cohort of patients with CANVAS includes six sibling pairs, which points to a genetic component for inheritance of the disease. The frequency of the disease is yet to be established, and identification of the culprit gene is currently a target of investigation.

*Szmulewicz DJ, McLean CA, Rodriguez ML, Chancellor AM, Mossman S, Lamont D, Roberts L, Storey E, Halmagyi GM. Dorsal root ganglionopathy is responsible for the sensory impairment in CANVAS. Neurology 2014;82(16);1410-5.

In collaboration with The Florey Institute of Neuroscience and Mental Health, we published a paper in the **American Journal of Human Genetics outlining a novel mutation in RAB39B as a cause for X-linked intellectual disability and early-onset Parkinson’s Disease (PD) with α-synuclein pathology.

Genetic analysis demonstrating the RAB39B mutation correlated with post mortem pathological studies confirming PD. Additional work in the paper outlined mechanisms of disease and the potential for significant advances in an understanding of the mechanism of sporadic PD.

**Wilson GR , Sim JC, McLean C et al., Mutations in RAB39B cause X-linked intellectual disability and early-onset Parkinson disease with α-synuclein pathology. Am J Hum Genet 2014;95(6):729-35.