An Updated Canvas of the RFC1-mediated CANVAS (Cerebellar Ataxia, Neuropathy and Vestibular Areflexia Syndrome)

• Published in: Molecular neurobiology Vol. 62; no. 1; pp. 693 - 707
• Main Authors: Shukla, Sakshi, Gupta, Kanav, Singh, Krishna, Mishra, Amit, Kumar, Amit
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.01.2025; Springer Nature B.V
• Subjects: Animals; Ataxia; Bilateral Vestibulopathy - epidemiology; Bilateral Vestibulopathy - genetics; Bilateral Vestibulopathy - pathology; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cerebellar ataxia; Cerebellar Ataxia - epidemiology; Cerebellar Ataxia - genetics; Cerebellar Ataxia - pathology; Cerebellum; Epidemiology; Hereditary diseases; Humans; Molecular modelling; Neurobiology; Neurodegenerative diseases; Neurology; Neuropathy; Neurosciences; Peripheral Nervous System Diseases - epidemiology; Peripheral Nervous System Diseases - genetics; Peripheral Nervous System Diseases - pathology; Replication Protein C - genetics; Replication Protein C - metabolism; Review; Vestibular system; Repeat expansion; Neurodegenerative disease; RFC1; CANVAS; AAGGG
• ISSN: 0893-7648; 1559-1182; 1559-1182
• DOI: 10.1007/s12035-024-04307-0

Proliferation of specific nucleotide sequences within the coding and non-coding regions of numerous genes has been implicated in approximately 40 neurodegenerative disorders. Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), a neurodegenerative disorder, is distinguished by a pathological triad of sensory neuropathy, bilateral vestibular areflexia and cerebellar impairments. It manifests in adults gradually and is autosomal recessive and multi-system ataxia. Predominantly, CANVAS is associated with biallelic AAGGG repeat expansions in intron 2 of the RFC1 gene. Although various motifs have been identified, only a subset induces pathological consequences, by forming stable secondary structures that disrupt gene functions both in vitro and in vivo. The pathogenesis of CANVAS remains a subject of intensive research, yet its precise mechanisms remain elusive. Herein, we aim to comprehensively review the epidemiology, clinical ramifications, molecular mechanisms, genetics, and potential therapeutics in light of the current findings, extending an overview of the most significant research on CANVAS.