Biallelic expansion of an intronic repeat in the RFC1 gene in a sample of Brazilian citizens: a genetic study

• Grant number: 19/20501-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2020
• End date: December 31, 2021
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Wilson Marques Junior
• Grantee: Manoella Guerra de Albuquerque Bueno
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a late-onset, slowly progressive neurological disorder characterized by imbalance, sensory neuropathy and occasionally chronic cough and autonomic dysfunction. Despite recently described, being recognized as a well-defined clinical entity only in 2011, its etiopathogenesis is already on the process of elucidation due to the identification of a biallelic intronic AAGGG repeat expansion in the RFC1 gene which was carried by 100% of patients with familial CANVAS disease and 22% of the ones with late-onset ataxia. These numbers suggest a prevalence similar to Friedreich's ataxia, the most frequent early-onset recessive cerebellar ataxia. If these findings are confirmed, it will be possible to offer a definite diagnosis and genetic counseling for a large number of patients with late onset idiopathic cerebellar ataxia. This study aims to evaluate the AAGGG repeat expansion prevalence in a group of normal Brazilian individuals and in patients with late-onset ataxia, and the other clinical aspects of CANVAS. This will allow a definite diagnosis and genetic counseling for the patient and his family.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

REZENDE, THIAGO J. R.; SCHMITT, GABRIEL S.; DE LIMA, FABRICIO D.; DE BRITO, MARIANA RABELO; MATOS, PAULA CAMILA A. A. P.; BONADIA, LUCIANA CARDOSO; MARTINEZ, ALBERTO R. M.; CENDES, FERNANDO; PEDROSO, JOSE LUIZ; BARSOTTINI, ORLANDO G. P.; et al. RFC1-Related Disorder: In Vivo Evaluation of Spinal Cord Damage. MOVEMENT DISORDERS, v. 37, n. 10, p. 7-pg., 2022-07-25. (13/07559-3, 19/20501-0)

MATOS, PAULA CAMILA A. A. P.; REZENDE, THIAGO J. R.; SCHMITT, GABRIEL S.; BONADIA, LUCIANA CARDOSO; REIS, FABIANO; MARTINEZ, ALBERTO R. M.; DE LIMA, FABRICIO D.; BUENO, MANOELLA GUERRA DE ALBUQUERQUE; TOMASELLI, PEDRO JOSE; CENDES, FERNANDO; et al. Brain Structural Signature of RFC1-Related Disorder. MOVEMENT DISORDERS, v. 36, n. 11, JUL 2021. (19/20501-0, 13/07559-3, 17/13102-7)