Frequency of GAA- FGF14 Ataxia in a Large Cohort of Brazilian Patients With Unsolved Adult-Onset Cerebellar Ataxia

Luiz Eduardo Novis; Rodrigo S Frezatti; David Pellerin; Pedro J Tomaselli; Shahryar Alavi; Marcus Vinícius Della Coleta; Mariana Spitz; Marie-Josée Dicaire; Pablo Iruzubieta; José Luiz Pedroso; Orlando Barsottini; Andrea Cortese; Matt C Danzi; Marcondes C França Jr; Bernard Brais; Stephan Zuchner; Henry Houlden; Salmo Raskin; Wilson Marques; Helio A Teive

doi:10.1212/NXG.0000000000200094

Frequency of GAA- FGF14 Ataxia in a Large Cohort of Brazilian Patients With Unsolved Adult-Onset Cerebellar Ataxia

Neurol Genet. 2023 Aug 28;9(5):e200094. doi: 10.1212/NXG.0000000000200094. eCollection 2023 Oct.

Authors

Luiz Eduardo Novis¹, Rodrigo S Frezatti¹, David Pellerin¹, Pedro J Tomaselli¹, Shahryar Alavi¹, Marcus Vinícius Della Coleta¹, Mariana Spitz¹, Marie-Josée Dicaire¹, Pablo Iruzubieta¹, José Luiz Pedroso¹, Orlando Barsottini¹, Andrea Cortese¹, Matt C Danzi¹, Marcondes C França Jr¹, Bernard Brais¹, Stephan Zuchner¹, Henry Houlden¹, Salmo Raskin¹, Wilson Marques¹, Helio A Teive¹

Affiliation

¹ From the Pós-graduação Em Medicina Interna e Ciências da Saúde (L.E.N., H.A.T.), Hospital de Clínicas da Universidade Federal do Paraná, Curitiba, Brazil; Department of Neuromuscular Diseases (L.E.N., D.P., S.A., P.I., A.C., H.H.), UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery, London, UK; Department of Neurology (R.S.F., P.J.T., W.M.), School of Medicine at Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil; Departments of Neurology and Neurosurgery (D.P., M.-J.D., B.B.), Montreal Neurological Hospital and Institute, McGill University, Canada; Departamento de Neurologia (M.V.D.C.), Universidade do Estado do Amazonas, Manaus; Departamento de Especialidades Médicas (M.S.), Serviço de Neurologia, Universidade Estadual do Rio de Janeiro, Brazil; Department of Neurology (P.I.), Donostia University Hospital; Neuroscience Area (P.I.), Biodonostia Health Research Institute, San Sebastian; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED) (P.I.), Spain; Department of Neurology (J.L.P., O.B.), Ataxia Unit, Universidade Federal de São Paulo, SP, Brazil; Department of Brain and Behavioral Sciences (A.C.), University of Pavia, Italy; Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics (M.C.D., S.Z.), University of Miami Miller School of Medicine; Department of Neurology (M.C.F.), School of Medical Sciences-University of Campinas (UNICAMP), São Paulo, Brazil; Department of Human Genetics (B.B.), McGill University, Montreal, Canada; and Laboratório Genetika (S.R.), Curitiba, PR, Brazil.

Abstract

Objectives: Intronic FGF14 GAA repeat expansions have recently been found to be a common cause of hereditary ataxia (GAA-FGF14 ataxia; SCA27B). The global epidemiology and regional prevalence of this newly reported disorder remain to be established. In this study, we investigated the frequency of GAA-FGF14 ataxia in a large cohort of Brazilian patients with unsolved adult-onset ataxia.

Methods: We recruited 93 index patients with genetically unsolved adult-onset ataxia despite extensive genetic investigation and genotyped the FGF14 repeat locus. Patients were recruited across 4 different regions of Brazil.

Results: Of the 93 index patients, 8 (9%) carried an FGF14 (GAA)_≥250 expansion. The expansion was also identified in 1 affected relative. Seven patients were of European descent, 1 was of African descent, and 1was of admixed American ancestry. One patient carrying a (GAA)₃₇₆ expansion developed ataxia at age 28 years, confirming that GAA-FGF14 ataxia can occur before the age of 30 years. One patient displayed episodic symptoms, while none had downbeat nystagmus. Cerebellar atrophy was observed on brain MRI in 7 of 8 patients (87%).

Discussion: Our results suggest that GAA-FGF14 ataxia is a common cause of adult-onset ataxia in the Brazilian population, although larger studies are needed to fully define its epidemiology.