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A new dominantly inherited pure cerebellar ataxia, SCA 30
  1. E Storey1,
  2. M Bahlo2,
  3. M Fahey3,4,
  4. O Sisson2,5,
  5. C J Lueck6,
  6. R J M Gardner3
  1. 1
    Department of Neuroscience, Monash University Department of Medicine (Alfred Hospital Campus), Melbourne, Australia
  2. 2
    Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
  3. 3
    Genetic Health Services Victoria, Royal Children’s Hospital, and University of Melbourne Department of Paediatrics, Melbourne, Australia
  4. 4
    Department of Neurology, Monash Medical Centre, and Monash University Department of Paediatrics, Melbourne, Australia
  5. 5
    Department of Mathematics and Statistics, Melbourne University, Melbourne, Australia
  6. 6
    Department of Neurology, The Canberra Hospital, and Australian National University, Canberra, Australia
  1. Professor E Storey, Department of Neuroscience, Alfred Hospital, Commercial Road, Melbourne, VIC 3004, Australia; elsdon.storey{at}med.monash.edu.au

Abstract

Background: The spinocerebellar ataxias (SCAs) are clinically and genetically heterogeneous. Currently, 27 forms are known, with the causative gene identified in 16. Although the majority of dominant pedigrees worldwide have SCAs 1, 2, 3, 6 or 8, new SCAs continue to be delineated. We describe a new disorder: SCA 30.

Methods: An Australian family of Anglo-Celtic ethnicity manifested a relatively pure, slowly evolving ataxia. Six affected and four unaffected members were personally examined in a standardised fashion. MRI and nerve conduction studies were performed in two. An autosomal genome-wide linkage study was undertaken, and an in silico analysis of potential candidate genes in the linkage region was performed.

Results: The six affected members had a relatively pure, slowly evolving ataxia developing in mid to late life, with only minor pyramidal signs and no evidence of neuropathy. All had hypermetric saccades with normal vestibulo-ocular reflex gain. Only one displayed (slight) gaze-evoked nystagmus. MRI showed cerebellar atrophy with preservation of nodulus/uvula and brainstem. Linkage analysis excluded currently known SCAs and identified a logarithm (base 10) of odds score of 3.0 at chromosome 4q34.3–q35.1, distinct from all previously reported loci. In silico prioritisation identified the gene ODZ3 as the most likely contender.

Conclusions: SCA 30 is a previously undescribed cause of (relatively) pure adult-onset autosomal dominant cerebellar ataxia. The responsible gene is yet to be determined, but ODZ3 is a plausible candidate.

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Footnotes

  • Competing interests: None.

  • Funding: ES is supported by the Van Cleef Roet Centre, Monash University, MB by an NH & MRC Career Development Award, and OS by the Undergraduate Research Opportunities Program (UROP). MF and RJMG have had support from the Murdoch Children’s Research Institute. CL is supported by the Canberra Hospital.

  • Ethics approval: Ethics approval was obtained from the Royal Children’s Hospital Human Ethics Committee.

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