Brain Structural Signature of RFC1-Related Disorder

Author(s):Show less -

Matos, Paula Camila A. A. P. ^{[1, 2]} ; Rezende, Thiago J. R. ^[3] ; Schmitt, Gabriel S. ^[3] ; Bonadia, Luciana Cardoso ^[4] ; Reis, Fabiano ^[5] ; Martinez, Alberto R. M. ^[3] ; de Lima, Fabricio D. ^[3] ; Bueno, Manoella Guerra de Albuquerque ^[6] ; Tomaselli, Pedro Jose ^[6] ; Cendes, Fernando ^[3] ; Pedroso, Jose Luiz ^{[1, 2]} ; Barsottini, Orlando G. P. ^{[1, 2]} ; Marques Jr, Wilson ; Franca Jr, MarcondesCavalcante

Affiliation

^[1] Fed Univ Sao Paulo UNIFESP, Dept Neurol, Div Gen Neurol, Sao Paulo, SP - Brazil

^[2] Fed Univ Sao Paulo UNIFESP, Dept Neurol, Ataxia Unit, Sao Paulo, SP - Brazil

^[3] Univ Campinas UNICAMP, Sch Med Sci, Dept Neurol, Campinas - Brazil

^[4] Univ Campinas UNICAMP, Sch Med Sci, Dept Med Genet, Campinas - Brazil

^[5] Univ Campinas UNICAMP, Sch Med Sci, Dept Radiol, Campinas - Brazil

^[6] Univ Sao Paulo USP Ribeirao Preto, Sch Med, Dept Neuroscience & Behav Sci, Ribeirao Preto - Brazil

• Document type: Journal article
• Source: MOVEMENT DISORDERS; v. 36, n. 11 JUL 2021.
• Web of Science Citations: 0

Abstract

Background The cerebellar ataxia, neuropathy, and vestibular areflexia syndrome was initially described in the early 1990s as a late-onset slowly progressive condition. Its underlying genetic cause was recently mapped to the RFC1 gene, and additional reports have expanded on the phenotypic manifestations related to RFC1, although little is known about the pattern and extent of structural brain abnormalities in this condition. Objective The aim is to characterize the structural signature of brain damage in RFC1-related disorder, correlating the findings with clinical symptoms and normal brain RFC1 expression. Methods We recruited 22 individuals with molecular confirmation of RFC1 expansions and submitted them to high-resolution 3T magnetic resonance imaging scans. We performed multimodal analyses to assess separately cerebral and cerebellar abnormalities within gray and white matter (WM). The results were compared with a group of 22 age- and sex-matched controls. Results The mean age and disease duration of patients were 62.8 and 10.9 years, respectively. Ataxia, sensory neuronopathy, and vestibular areflexia were the most frequent manifestations, but parkinsonism and pyramidal signs were also noticed. We found that RFC1-related disorder is characterized by widespread and relatively symmetric cerebellar and basal ganglia atrophy. There is brainstem volumetric reduction along all its segments. Cerebral WM is also involved-mostly the corpus callosum and deep tracts, but cerebral cortical damage is rather restricted. Conclusion This study adds new relevant insights into the pathophysiological mechanisms of RFC1-related disorder. It should no longer be considered a purely cerebellar and sensory pathway disorder. Basal ganglia and deep cerebral WM are additional targets of damage. (c) 2021 International Parkinson and Movement Disorder Society (AU)

• FAPESP's process: 19/20501-0 - Biallelic expansion of an intronic repeat in the RFC1 gene in a sample of Brazilian citizens: a genetic study
• Grantee: Manoella Guerra de Albuquerque Bueno
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 13/07559-3 - BRAINN - The Brazilian Institute of Neuroscience and Neurotechnology
• Grantee: Fernando Cendes
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 17/13102-7 - Characterization and Comparison of Bayesian and Deep Learning based Methods for Cerebellar Segmentation
• Grantee: Thiago Junqueira Ribeiro de Rezende
• Support Opportunities: Scholarships in Brazil - Post-Doctoral