Session Information
Date: Monday, September 23, 2019
Session Title: Ataxia
Session Time: 1:45pm-3:15pm
Location: Les Muses, Level 3
Objective: To identify and characterize the genetic cause of common, idiopathic, cerebellar ataxia.
Background: Late-onset ataxia is a common reason for neurological consultation, but its cause often remains idiopathic. Cerebellar dysfunction, but also proprioceptive or vestibular impairment, can lead to ataxia. When in combination, this more severe type of ataxia is termed cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). Both sporadic and familial cases of CANVAS have been reported, suggesting the possibility of a recessive transmission of the disease. The a of this study was to identify the genetic cause of CANVAS and sensory ataxia.
Method: We performed non-parametric linkage analysis and genome sequencing. The presence of the repeat expansion was confirmed by repeat-primed PCR, long-range PCR and southern blot. Functional studies were performed to assess the effect of the repeat expansion on the expression of the repeat-hosting gene.
Results: We identified an intronic recessive repeat expansion in as the cause of CANVAS and a common cause of late-onset sensory ataxia. The recessive repeat expansion, ranging in patients from 400 to several thousand repeats, showed full segregation in 23 cases from 11 families. Additionally, 33 (22%) out of 150 sporadic cases with late-onset ataxia from a single-centre carried the recessive repeat expansion. The percentage raised to 62% in patients with sensory neuronopathy and cerebellar involvement and 92% in full-blown CANVAS disease. Notably, the pentanucleotide repeat expansion does not affect expression of the repeat hosting gene at mRNA and protein levels in patient fibroblasts.
Conclusion: These data, together with the observation of an carrier frequency of the expanded repeat of 0.7% the European population, suggesting that this pentanucleotide repeat expansion represents a frequent cause of late-onset ataxia and raises the possibility of unconventional disease-causing mechanisms in this late-onset recessive disorder.
To cite this abstract in AMA style:
H. Houlden, M. Reilly, S. Zuchner, W. Marques, P. Fratta, A. Bronstein, A. Rossor, A. Rebelo, E. Buglo, N. Andrade, N. Wood, D. Kaski, S. Efthymiou, V. Salpietro, M. Versino, I. Callegari, D. Devigili, P. Tomaselli, E. Tribollet, M. Ilyas, J. Polke, P. Sivakumar, Z. Jaunmuktane, J. Humphrey, Y. Yan, H. Tariq, J. Vandrovcova, R. Sullivan, R. Simone, A. Cortese. A recessive repeat expansion causes CANVAS and is a common cause of Late-Onset Ataxia [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/a-recessive-repeat-expansion-causes-canvas-and-is-a-common-cause-of-late-onset-ataxia/. Accessed June 14, 2025.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/a-recessive-repeat-expansion-causes-canvas-and-is-a-common-cause-of-late-onset-ataxia/